HOME

TheInfoList



OR:

Actin is a
family Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...
of globular multi-functional
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s that form microfilaments in the
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 
kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
, with a diameter of 4 to 7 nm. An actin protein is the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major components of the cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells. It can be present as either a free monomer called G-actin (globular) or as part of a linear
polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
microfilament called F-actin (filamentous), both of which are essential for such important cellular functions as the
mobility Mobility may refer to: Social sciences and humanities * Economic mobility, ability of individuals or families to improve their economic status * Geographic mobility, the measure of how populations and goods move over time * Mobilities, a conte ...
and contraction of cells during
cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
. Actin participates in many important cellular processes, including muscle contraction, cell
motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
, cell division and cytokinesis, vesicle and organelle movement,
cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
, and the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes. In vertebrates, three main groups of actin isoforms, alpha, beta, and gamma have been identified. The alpha actins, found in muscle tissues, are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
, and as mediators of internal cell
motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
. It is believed that the diverse range of structures formed by actin enabling it to fulfill such a large range of functions is regulated through the binding of tropomyosin along the filaments. A cell's ability to dynamically form microfilaments provides the scaffolding that allows it to rapidly remodel itself in response to its environment or to the organism's internal
signals In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...
, for example, to increase cell membrane absorption or increase cell adhesion in order to form cell tissue. Other enzymes or organelles such as cilia can be anchored to this scaffolding in order to control the deformation of the external
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, which allows endocytosis and cytokinesis. It can also produce movement either by itself or with the help of molecular motors. Actin therefore contributes to processes such as the intracellular transport of vesicles and organelles as well as
muscular contraction Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as ...
and cellular migration. It therefore plays an important role in embryogenesis, the healing of wounds, and the invasivity of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
cells. The evolutionary origin of actin can be traced to
prokaryotic cells A prokaryote () is a Unicellular organism, single-celled organism that lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek language, Greek wikt:πρό#Ancient Greek, πρό (, 'before') a ...
, which have equivalent proteins. Actin homologs from prokaryotes and archaea polymerize into different helical or linear filaments consisting of one or multiple strands. However the in-strand contacts and nucleotide binding sites are preserved in prokaryotes and in archaea. Lastly, actin plays an important role in the control of gene expression. A large number of illnesses and diseases are caused by mutations in
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
s of the
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s that regulate the production of actin or of its associated proteins. The production of actin is also key to the process of
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
by some
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
ic microorganisms. Mutations in the different genes that regulate actin production in humans can cause muscular diseases, variations in the size and function of the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
as well as deafness. The make-up of the cytoskeleton is also related to the pathogenicity of intracellular
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
and
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es, particularly in the processes related to evading the actions of the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
.


Function

Actin's primary role in the cell is to form linear polymers called microfilaments that serve various functions in the cell's structure, trafficking networks, migration, and replication. The multifaceted role of actin relies on a few of the microfilaments' properties: First, the formation of actin filaments is reversible, and their function often involves undergoing rapid polymerization and depolymerization. Second, microfilaments are polarized – i.e. the two ends of a filament are distinct from one another. Third, actin filaments can bind to many other proteins, which together help modify and organize microfilaments for their diverse functions. In most cells actin filaments form larger-scale networks which are essential for many key functions: * Actin networks give mechanical support to cells and provide trafficking routes through the cytoplasm to aid signal transduction. * Rapid assembly and disassembly of actin network enables cells to migrate ( Cell migration). Actin is extremely abundant in most cells, comprising 1–5% of the total protein mass of most cells, and 10% of muscle cells. The actin protein is found in both the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
and the cell nucleus. Its location is regulated by cell membrane signal transduction pathways that integrate the stimuli that a cell receives stimulating the restructuring of the actin networks in response.


Cytoskeleton

There are a number of different types of actin with slightly different structures and functions. α-actin is found exclusively in
muscle fibre A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscle ...
s, while β- and γ-actin are found in other cells. As the latter types have a high turnover rate the majority of them are found outside permanent structures. Microfilaments found in cells other than muscle cells are present in three forms: * Microfilament networks - Animal cells commonly have a cell cortex under the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
that contains a large number of microfilaments, which precludes the presence of organelles. This network is connected with numerous receptors that relay signals to the outside of a cell. * Periodic actin rings - A periodic structure constructed of evenly spaced actin rings is found in
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s. In this structure, the actin rings, together with
spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...
tetramers that link the neighboring actin rings, form a cohesive
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
that supports the axon membrane. The structure periodicity may also regulate the
sodium ion channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
s in axons.


Yeasts

Actin's cytoskeleton is key to the processes of endocytosis, cytokinesis, determination of cell polarity and
morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...
in
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
s. In addition to relying on actin, these processes involve 20 or 30 associated proteins, which all have a high degree of evolutionary conservation, along with many signalling molecules. Together these elements allow a spatially and temporally modulated assembly that defines a cell's response to both internal and external stimuli. Yeasts contain three main elements that are associated with actin: patches, cables, and rings. Despite not being present for long, these structures are subject to a dynamic equilibrium due to continual polymerization and depolymerization. They possess a number of accessory proteins including ADF/cofilin, which has a molecular weight of 16kDa and is coded for by a single gene, called ''COF1''; Aip1, a cofilin cofactor that promotes the disassembly of microfilaments; Srv2/CAP, a process regulator related to
adenylate cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...
proteins; a profilin with a molecular weight of approximately 14 kDa that is related/associated with actin monomers; and twinfilin, a 40 kDa protein involved in the organization of patches.


Plants

Plant
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
studies have revealed the existence of protein isovariants within the actin family of genes. Within '' Arabidopsis thaliana'', a model organism, there are ten types of actin, six profilins, and dozens of myosins. This diversity is explained by the evolutionary necessity of possessing variants that slightly differ in their temporal and spatial expression. The majority of these proteins were jointly expressed in the tissue analysed. Actin networks are distributed throughout the cytoplasm of cells that have been cultivated ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
''. There is a concentration of the network around the nucleus that is connected via spokes to the cellular cortex, this network is highly dynamic, with a continuous polymerization and depolymerization. Even though the majority of plant cells have a cell wall that defines their morphology, their microfilaments can generate sufficient force to achieve a number of cellular activities, such as the cytoplasmic currents generated by the microfilaments and myosin. Actin is also involved in the movement of organelles and in cellular morphogenesis, which involve
cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
as well as the elongation and differentiation of the cell. The most notable proteins associated with the actin cytoskeleton in plants include: villin, which belongs to the same family as gelsolin/severin and is able to cut microfilaments and bind actin monomers in the presence of calcium cations;
fimbrin Fimbrin also known as is plastin 1 is a protein that in humans is encoded by the PLS1 gene. Fimbrin is an actin cross-linking protein important in the formation of filopodia. Structure Fimbrin belongs to the calponin homology (CH) domain supe ...
, which is able to recognize and unite actin monomers and which is involved in the formation of networks (by a different regulation process from that of animals and yeasts); formins, which are able to act as an F-actin polymerization nucleating agent; myosin, a typical molecular motor that is specific to eukaryotes and which in ''Arabidopsis thaliana'' is coded for by 17 genes in two distinct classes; CHUP1, which can bind actin and is implicated in the spatial distribution of chloroplasts in the cell; KAM1/MUR3 that define the morphology of the
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...
as well as the composition of xyloglucans in the cell wall; NtWLIM1, which facilitates the emergence of actin cell structures; and ERD10, which is involved in the association of organelles within membranes and microfilaments and which seems to play a role that is involved in an organism's reaction to
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
.


Nuclear actin

Nuclear actin was first noticed and described in 1977 by Clark and Merriam. Authors describe a protein present in the nuclear fraction, obtained from ''Xenopus laevis'' oocytes, which shows the same features as skeletal muscle actin. Since that time there have been many scientific reports about the structure and functions of actin in the nucleus (for review see: Hofmann 2009.) The controlled level of actin in the nucleus, its interaction with actin-binding proteins (ABP) and the presence of different isoforms allows actin to play an important role in many important nuclear processes.


Transport through the nuclear membrane

The actin sequence does not contain a nuclear localization signal. The small size of actin (about 43 kDa) allows it to enter the nucleus by passive diffusion. The import of actin into the nucleus (probably in a complex with cofilin) is facilitated by the import protein importin 9. Low levels of actin in the nucleus seems to be important, because actin has two nuclear export signals (NES) in its sequence. Microinjected actin is quickly removed from the nucleus to the cytoplasm. Actin is exported at least in two ways, through exportin 1 and exportin 6. Specific modifications, such as SUMOylation, allows for nuclear actin retention. A mutation preventing SUMOylation causes rapid export of beta actin from the nucleus.


Organization

Nuclear actin exists mainly as a monomer, but can also form dynamic oligomers and short polymers. Nuclear actin organization varies in different cell types. For example, in ''Xenopus'' oocytes (with higher nuclear actin level in comparison to somatic cells) actin forms filaments, which stabilize nucleus architecture. These filaments can be observed under the microscope thanks to fluorophore-conjugated phalloidin staining. In somatic cell nuclei, however, actin filaments cannot be observed using this technique. The DNase I inhibition assay, the only test which allows the quantification of the polymerized actin directly in biological samples, has revealed that endogenous nuclear actin indeed occurs mainly in a monomeric form. Precisely controlled level of actin in the cell nucleus, lower than in the cytoplasm, prevents the formation of filaments. The polymerization is also reduced by the limited access to actin monomers, which are bound in complexes with ABPs, mainly cofilin.


Actin isoforms

Different isoforms of actin are present in the cell nucleus. The level of actin isoforms may change in response to stimulation of cell growth or arrest of proliferation and transcriptional activity. Research on nuclear actin is focused on isoform beta. However the use of antibodies directed against different actin isoforms allows identifying not only the cytoplasmic beta in the cell nucleus, but also alpha- and gamma-actin in certain cell types. The presence of different isoforms of actin may have a significant effect on its function in nuclear processes, as the level of individual isoforms can be controlled independently.


Functions

Functions of actin in the nucleus are associated with its ability to polymerize and interact with various ABPs and with structural elements of the nucleus. Nuclear actin is involved in: * Architecture of the nucleus - Interaction of actin with alpha II-spectrin and other proteins are important for maintaining proper shape of the nucleus. * Transcription – Actin is involved in chromatin reorganization, transcription initiation and interaction with the transcription complex. Actin takes part in the regulation of chromatin structure, interacting with RNA polymerase I, II and III. In Pol I transcription, actin and myosin ( MYO1C, which binds DNA) act as a molecular motor. For Pol II transcription, β-actin is needed for the formation of the preinitiation complex. Pol III contains β-actin as a subunit. Actin can also be a component of chromatin remodelling complexes as well as pre-mRNP particles (that is, precursor messenger RNA bundled in proteins), and is involved in nuclear export of RNAs and proteins. * Regulation of gene activity – Actin binds to the regulatory regions of different kinds of genes. Actin's ability to regulate gene activity is used in the molecular reprogramming method, which allows differentiated cells return to their embryonic state. * Translocation of the activated chromosome fragment from under membrane region to euchromatin where transcription starts. This movement requires the interaction of actin and myosin. * Integration of different cellular compartments. Actin is a molecule that integrates cytoplasmic and nuclear signal transduction pathways. An example is the activation of transcription in response to serum stimulation of cells ''in vitro''. * Immune response - Nuclear actin polymerizes upon
T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...
stimulation and is required for cytokine expression and antibody production ''in vivo''. Due to its ability to undergo conformational changes and interaction with many proteins, actin acts as a regulator of formation and activity of protein complexes such as transcriptional complex.


Cell movement

Actin is also involved in cell movement. A meshwork of actin filaments marks the forward edge of a moving cell, and the polymerization of new actin filaments pushes the cell membrane forward in protrusions called lamellipodia. These membrane protrusions then attach to the substrate, forming structures known as
focal adhesions In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...
that connect to the actin network. Once attached, the rear of the cell body contracts squeezing its contents forward past the adhesion point. Once the adhesion point has moved to the rear of the cell, the cell disassembles it, allowing the rear of the cell to move forward.


Actin/myosin movement

In addition to the physical force generated by actin polymerization, microfilaments facilitate the movement of various intracellular components by serving as the roadway along which a family of motor proteins called myosins travel.


Muscle contraction

Actin plays a particularly prominent role in muscle cells, which consist largely of repeated bundles of actin and
myosin II Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin (M2 ...
. Each repeated unit – called a
sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...
– consists of two sets of oppositely oriented F-actin strands ("thin filaments"), interlaced with bundles of myosin ("thick filaments"). The two sets of actin strands are oriented with their (+) ends embedded in either end of the sarcomere in delimiting structures called
Z-disk A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called musc ...
s. The myosin fibrils are in the middle between the sets of actin filaments, with strands facing in both directions. When the muscle contracts, the myosin threads move along the actin filaments towards the (+) end, pulling the ends of the sarcomere together and shortening it by around 70% of its length. In order to move along the actin thread, myosin must hydrolyze ATP; thus ATP serves as the energy source for muscle contraction. At times of rest, the proteins tropomyosin and
troponin image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL Troponin, ...
bind to the actin filaments, preventing the attachment of myosin. When an activation signal (i.e. an
action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
) arrives at the muscle fiber, it triggers the release of Ca2+ from the
sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...
into the cytosol. The resulting spike in cytosolic calcium rapidly releases tropomyosin and troponin from the actin thread, allowing myosin to bind, and muscle contracation to begin.


Cell division

In the final stages of
cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
, many cells form a ring of actin at the cell's midpoint. This ring, aptly called the "
contractile ring In molecular biology, an actomyosin contractile ring is a prominent structure during cytokinesis.Cheffings TH, Burroughs NJ, Balasubramanian MK. (2016). Actomyosin Ring Formation and Tension Generation in Eukaryotic Cytokinesis. Curr Biol. 26(15): ...
", uses a similar mechanism as muscle fibers where myosin II pulls along the actin ring, causing it to contract. This contraction cleaves the parent cell into two, completing cytokinesis. The contractile ring is composed of actin, myosin, anillin, and
α-actinin Actinin is a microfilament protein. Alpha-actinin-1 is necessary for the attachment of actin myofilaments to the Sarcomere, Z-lines in Skeletal muscle, skeletal muscle cells, and to the Smooth muscle tissue, dense bodies in smooth muscle cells. The ...
. In the fission yeast ''
Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...
'', actin is actively formed in the constricting ring with the participation of Arp3, the formin Cdc12, profilin, and
WASp A wasp is any insect of the narrow-waisted suborder Apocrita of the order Hymenoptera which is neither a bee nor an ant; this excludes the broad-waisted sawflies (Symphyta), which look somewhat like wasps, but are in a separate suborder. ...
, along with preformed microfilaments. Once the ring has been constructed the structure is maintained by a continual assembly and disassembly that, aided by the Arp2/3 complex and formins, is key to one of the central processes of cytokinesis.


Intracellular trafficking

Actin-myosin pairs can also participate in the trafficking of various membrane vesicles and organelles within the cell. Myosin V is activated by binding to various cargo receptors on organelles, and then moves along an actin filament towards the (+) end, pulling its cargo along with it. These nonconventional myosins use ATP hydrolysis to transport cargo, such as vesicles and organelles, in a directed fashion much faster than diffusion. Myosin V walks towards the barbed end of actin filaments, while myosin VI walks toward the pointed end. Most actin filaments are arranged with the barbed end toward the cellular membrane and the pointed end toward the cellular interior. This arrangement allows myosin V to be an effective motor for the export of cargos, and myosin VI to be an effective motor for import.


Other biological processes

The traditional image of actin's function relates it to the maintenance of the cytoskeleton and, therefore, the organization and movement of organelles, as well as the determination of a cell's shape. However, actin has a wider role in eukaryotic cell physiology, in addition to similar functions in
prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Conne ...
s. * Apoptosis. During
programmed cell death Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers ...
the ICE/ced-3 family of proteases (one of the interleukin-1β-converter proteases) degrade actin into two fragments ''in vivo''; one of the fragments is 15 kDa and the other 31 kDa. This represents one of the mechanisms involved in destroying cell viability that form the basis of apoptosis. The protease
calpain A calpain (; , ) is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases ( proteolytic enzymes) expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan C ...
has also been shown to be involved in this type of cell destruction; just as the use of calpain inhibitors has been shown to decrease actin proteolysis and the degradation of DNA (another of the characteristic elements of apoptosis). On the other hand, the
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
-induced triggering of apoptosis causes the reorganization of the actin cytoskeleton (which also involves its polymerization), giving rise to structures called
stress fiber Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated ...
s; this is activated by the MAP kinase pathway. *
Cellular adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indire ...
and
development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...
. The adhesion between cells is a characteristic of
multicellular organisms A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni ...
that enables tissue specialization and therefore increases cell complexity. Adhesion of cell
epithelia Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
involves the actin cytoskeleton in each of the joined cells as well as cadherins acting as extracellular elements with the connection between the two mediated by
catenin Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as α-catenin and β-catenin. α-Catenin can bind to β-catenin and can also bind ...
s. Interfering in actin dynamics has repercussions for an organism's development, in fact actin is such a crucial element that systems of redundant
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s are available. For example, if the
α-actinin Actinin is a microfilament protein. Alpha-actinin-1 is necessary for the attachment of actin myofilaments to the Sarcomere, Z-lines in Skeletal muscle, skeletal muscle cells, and to the Smooth muscle tissue, dense bodies in smooth muscle cells. The ...
or
gelation In polymer chemistry, gelation (gel transition) is the formation of a gel from a system with polymers. Branched polymers can form links between the chains, which lead to progressively larger polymers. As the linking continues, larger branched p ...
factor gene has been removed in ''
Dictyostelium ''Dictyostelium'' is a genus of single- and multi-celled eukaryotic, phagotrophic bacterivores. Though they are Protista and in no way fungal, they traditionally are known as "slime molds". They are present in most terrestrial ecosystems ...
'' individuals do not show an anomalous
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
possibly due to the fact that each of the proteins can perform the function of the other. However, the development of double mutations that lack both gene types is affected. * Gene expression modulation. Actin's state of polymerization affects the pattern of gene expression. In 1997, it was discovered that cytocalasin D-mediated depolymerization in
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ens ...
s causes a specific pattern of expression for the genes involved in the myelinization of this type of
nerve cell A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...
. F-actin has been shown to modify the transcriptome in some of the life stages of unicellular organisms, such as the fungus ''
Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
''. In addition, proteins that are similar to actin play a regulatory role during spermatogenesis in mice and, in yeasts, actin-like proteins are thought to play a role in the regulation of gene expression. In fact, actin is capable of acting as a transcription initiator when it reacts with a type of nuclear myosin that interacts with RNA polymerases and other enzymes involved in the transcription process. *
Stereocilia Stereocilia (or stereovilli or villi) are non-motile apical cell modifications. They are distinct from cilia and microvilli, but are closely related to microvilli. They form single "finger-like" projections that may be branched, with normal cell ...
dynamics. Some cells develop fine filliform outgrowths on their surface that have a mechanosensory function. For example, this type of organelle is present in the Organ of Corti, which is located in the
ear An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...
. The main characteristic of these structures is that their length can be modified. The molecular architecture of the stereocilia includes a
paracrystalline In materials science, paracrystalline materials are defined as having short- and medium-range ordering in their lattice (similar to the liquid crystal phases) but lacking crystal-like long-range ordering at least in one direction. Origin and ...
actin core in dynamic equilibrium with the monomers present in the adjacent cytosol. Type VI and VIIa myosins are present throughout this core, while myosin XVa is present in its extremities in quantities that are proportional to the length of the stereocilia. * Intrinsic chirality. Actomyosin networks have been implicated in generating an intrinsic chirality in individual cells. Cells grown out on chiral surfaces can show a directional left/right bias that is actomyosin dependent.


Structure

Monomeric actin, or G-actin, has a globular structure consisting of two lobes separated by a deep cleft. The bottom of the cleft represents the “ATPase fold”, a structure conserved among ATP and GTP-binding proteins that binds to a magnesium ion and a molecule of ATP. Binding of ATP or ADP is required to stabilize each actin monomer; without one of these molecules bound, actin quickly becomes denatured. The
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
model of actin that was produced by Kabsch from the striated muscle tissue of rabbits is the most commonly used in structural studies as it was the first to be purified. The G-actin crystallized by Kabsch is approximately 67 x 40 x 37 Å in size, has a molecular mass of 41,785 Da and an estimated
isoelectric point The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). However, pI is also u ...
of 4.8. Its net charge at pH = 7 is -7. ;Primary structure Elzinga and co-workers first determined the complete
peptide sequence Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...
for this type of actin in 1973, with later work by the same author adding further detail to the model. It contains 374
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
residues. Its N-terminus is highly acidic and starts with an acetyled aspartate in its amino group. While its C-terminus is alkaline and is formed by a phenylalanine preceded by a cysteine, which has a degree of functional importance. Both extremes are in close proximity within the I-subdomain. An anomalous ''N''τ-methylhistidine is located at position 73. ;Tertiary structure — domains The tertiary structure is formed by two domains known as the large and the small, which are separated by a cleft centred around the location of the bond with ATP- ADP+ Pi. Below this there is a deeper notch called a “groove”. In the native state, despite their names, both have a comparable depth. The normal convention in
topological In mathematics, topology (from the Greek words , and ) is concerned with the properties of a geometric object that are preserved under continuous deformations, such as stretching, twisting, crumpling, and bending; that is, without closing ...
studies means that a protein is shown with the biggest domain on the left-hand side and the smallest domain on the right-hand side. In this position the smaller domain is in turn divided into two: subdomain I (lower position, residues 1–32, 70–144, and 338–374) and subdomain II (upper position, residues 33–69). The larger domain is also divided in two: subdomain III (lower, residues 145–180 and 270–337) and subdomain IV (higher, residues 181–269). The exposed areas of subdomains I and III are referred to as the “barbed” ends, while the exposed areas of domains II and IV are termed the “pointed" ends. This nomenclature refers to the fact that, due to the small mass of subdomain II actin is polar; the importance of this will be discussed below in the discussion on assembly dynamics. Some authors call the subdomains Ia, Ib, IIa, and IIb, respectively. ;Other important structures The most notable supersecondary structure is a five chain beta sheet that is composed of a β-meander and a β-α-β clockwise unit. It is present in both domains suggesting that the protein arose from gene duplication. * The adenosine nucleotide binding site is located between two
beta hairpin The beta hairpin (sometimes also called beta-ribbon or beta-beta unit) is a simple protein structural motif involving two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in primary structure, oriented in ...
-shaped structures pertaining to the I and III domains. The residues that are involved are Asp11-Lys18 and Asp154-His161 respectively. * The divalent cation binding site is located just below that for the adenosine nucleotide. ''In vivo'' it is most often formed by Mg2+ or Ca2+ while ''in vitro'' it is formed by a chelating structure made up of Lys18 and two
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
s from the nucleotide's α-and β-
phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...
s. This calcium is coordinated with six water molecules that are retained by the amino acids Asp11, Asp154, and Gln137. They form a complex with the nucleotide that restricts the movements of the so-called "hinge" region, located between residues 137 and 144. This maintains the native form of the protein until its withdrawal denatures the actin monomer. This region is also important because it determines whether the protein's cleft is in the "open" or "closed" conformation. * It is highly likely that there are at least three other centres with a lesser affinity (intermediate) and still others with a low affinity for divalent cations. It has been suggested that these centres may play a role in the polymerization of actin by acting during the activation stage. * There is a structure in subdomain 2 that is called the “D-loop” because it binds with DNase I, it is located between the His40 and Gly48 residues. It has the appearance of a disorderly element in the majority of crystals, but it looks like a β-sheet when it is complexed with DNase I. It has been proposed that the key event in polymerization is probably the propagation of a conformational change from the centre of the bond with the nucleotide to this domain, which changes from a loop to a spiral. However, this hypothesis has been refuted by other studies.


F-actin

Under various conditions, G-actin molecules polymerize into longer threads called "filamentous-" or "F-actin". These F-actin threads are typically composed of two helical strands of actin wound around each other, forming a 7 to 9 nanometer wide helix that repeats every 72 nanometers (or every 14 G-actin subunits). In F-actin threads, G-actin molecules are all oriented in the same direction. The two ends of the F-actin thread are distinct from one another. At one end – designated the (−) end – the ATP-binding cleft of the terminal actin molecule is facing outward. At the opposite end – designated (+) – the ATP-binding cleft is buried in the filament, contacting the neighboring actin molecule. As F-actin threads grow, new molecules tend to join at the (+) end of an existing F-actin strand. Conversely, threads tend to shrink by shedding actin monomers from the strand's (-) end. Some proteins, such as
cofilin ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle contractio ...
appear to increase the angle of turn, but again this could be interpreted as the establishment of different structural states. These could be important in the polymerization process. There is less agreement regarding measurements of the turn radius and filament thickness: while the first models assigned a length of 25 Å, current X-ray diffraction data, backed up by cryo-electron microscopy suggests a length of 23.7 Å. These studies have shown the precise contact points between monomers. Some are formed with units of the same chain, between the "barbed" end on one monomer and the "pointed" end of the next one. While the monomers in adjacent chains make lateral contact through projections from subdomain IV, with the most important projections being those formed by the C-terminus and the hydrophobic link formed by three bodies involving residues 39–42, 201–203, and 286. This model suggests that a filament is formed by monomers in a "sheet" formation, in which the subdomains turn about themselves, this form is also found in the bacterial actin homologue MreB. The terms "pointed" and "barbed" referring to the two ends of the microfilaments derive from their appearance under transmission electron microscopy when samples are examined following a preparation technique called "decoration". This method consists of the addition of myosin S1 fragments to tissue that has been fixed with tannic acid. This myosin forms polar bonds with actin monomers, giving rise to a configuration that looks like arrows with feather fletchings along its shaft, where the shaft is the actin and the fletchings are the myosin. Following this logic, the end of the microfilament that does not have any protruding myosin is called the point of the arrow (- end) and the other end is called the barbed end (+ end). A S1 fragment is composed of the head and neck domains of
myosin II Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin (M2 ...
. Under physiological conditions, G-actin (the monomer form) is transformed to F-actin (the
polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
form) by ATP, where the role of ATP is essential. The helical F-actin filament found in muscles also contains a tropomyosin molecule, which is a 40 nanometre long protein that is wrapped around the F-actin helix. During the resting phase the tropomyosin covers the actin's active sites so that the actin-myosin interaction cannot take place and produce muscular contraction. There are other protein molecules bound to the tropomyosin thread, these are the
troponin image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL Troponin, ...
s that have three polymers:
troponin I Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to ac ...
,
troponin T Troponin T (shortened TnT or TropT) is a part of the troponin complex, which are proteins integral to the contraction of skeletal and heart muscles. They are expressed in skeletal and cardiac myocytes. Troponin T binds to tropomyosin and help ...
, and
troponin C Troponin C is a protein which is part of the troponin complex. It contains four calcium-binding EF hands, although different isoforms may have fewer than four functional calcium-binding subdomains. It is a component of thin filaments, along wi ...
. F-actin is both strong and dynamic. Unlike other
polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
s, such as DNA, whose constituent elements are bound together with covalent bonds, the monomers of actin filaments are assembled by weaker bonds. The lateral bonds with neighbouring monomers resolve this anomaly, which in theory should weaken the structure as they can be broken by thermal agitation. In addition, the weak bonds give the advantage that the filament ends can easily release or incorporate monomers. This means that the filaments can be rapidly remodelled and can change cellular structure in response to an environmental stimulus. Which, along with the biochemical mechanism by which it is brought about is known as the "assembly dynamic".


Folding

Actin can spontaneously acquire a large part of its
tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may i ...
. However, the way it acquires its fully functional form from its newly synthesized native form is special and almost unique in protein chemistry. The reason for this special route could be the need to avoid the presence of incorrectly folded actin monomers, which could be toxic as they can act as inefficient polymerization terminators. Nevertheless, it is key to establishing the stability of the cytoskeleton, and additionally, it is an essential process for coordinating the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
. CCT is required in order to ensure that folding takes place correctly. CCT is a group II chaperonin, a large protein complex that assists in the folding of other proteins. CCT is formed of a double ring of eight different subunits (hetero-octameric) and it differs from group I chaperonins like
GroEL GroEL is a protein which belongs to the chaperonin family of molecular chaperones, and is found in many bacteria. It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein com ...
, which is found in Eubacteria and in eukaryotic organelles, as it does not require a co-chaperone to act as a lid over the central
catalytic Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
cavity. Substrates bind to CCT through specific domains. It was initially thought that it only bound with actin and
tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
, although recent immunoprecipitation studies have shown that it interacts with a large number of polypeptides, which possibly function as substrates. It acts through ATP-dependent conformational changes that on occasion require several rounds of liberation and catalysis in order to complete a reaction. In order to successfully complete their folding, both actin and tubulin need to interact with another protein called
prefoldin Prefoldin (GimC) is a superfamily of proteins used in protein folding complexes. It is classified as a heterohexameric molecular chaperone in both archaea and eukarya, including humans. A prefoldin molecule works as a transfer protein in conjun ...
, which is a heterohexameric complex (formed by six distinct subunits), in an interaction that is so specific that the molecules have
coevolved In biology, coevolution occurs when two or more species reciprocally affect each other's evolution through the process of natural selection. The term sometimes is used for two traits in the same species affecting each other's evolution, as well ...
. Actin complexes with prefoldin while it is still being formed, when it is approximately 145
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s long, specifically those at the N-terminal. Different recognition sub-units are used for actin or tubulin although there is some overlap. In actin the subunits that bind with prefoldin are probably PFD3 and PFD4, which bind in two places one between residues 60–79 and the other between residues 170–198. The actin is recognized, loaded, and delivered to the cytosolic chaperonin (CCT) in an open conformation by the inner end of prefoldin's "tentacles” (see the image and note). The contact when actin is delivered is so brief that a tertiary complex is not formed, immediately freeing the prefoldin. The CCT then causes actin's sequential folding by forming bonds with its subunits rather than simply enclosing it in its cavity. This is why it possesses specific recognition areas in its apical β-domain. The first stage in the folding consists of the recognition of residues 245–249. Next, other determinants establish contact. Both actin and tubulin bind to CCT in open conformations in the absence of ATP. In actin's case, two subunits are bound during each conformational change, whereas for tubulin binding takes place with four subunits. Actin has specific binding sequences, which interact with the δ and β-CCT subunits or with δ-CCT and ε-CCT. After AMP-PNP is bound to CCT the substrates move within the chaperonin's cavity. It also seems that in the case of actin, the CAP protein is required as a possible cofactor in actin's final folding states. The exact manner by which this process is regulated is still not fully understood, but it is known that the protein PhLP3 (a protein similar to phosducin) inhibits its activity through the formation of a tertiary complex.


ATPase’s catalytic mechanism

Actin is an ATPase, which means that it is an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that hydrolyzes ATP. This group of enzymes is characterised by their slow reaction rates. It is known that this ATPase is “active”, that is, its speed increases by some 40,000 times when the actin forms part of a filament. A reference value for this rate of hydrolysis under ideal conditions is around 0.3 s−1. Then, the Pi remains bound to the actin next to the ADP for a long time, until it is cooperatively liberated from the interior of the filament. The exact molecular details of the catalytic mechanism are still not fully understood. Although there is much debate on this issue, it seems certain that a "closed" conformation is required for the hydrolysis of ATP, and it is thought that the residues that are involved in the process move to the appropriate distance. The glutamic acid Glu137 is one of the key residues, which is located in subdomain 1. Its function is to bind the water molecule that produces a nucleophilic attack on the ATP's γ-phosphate bond, while the nucleotide is strongly bound to subdomains 3 and 4. The slowness of the catalytic process is due to the large distance and skewed position of the water molecule in relation to the reactant. It is highly likely that the conformational change produced by the rotation of the domains between actin's G and F forms moves the Glu137 closer allowing its hydrolysis. This model suggests that the polymerization and ATPase's function would be decoupled straight away. The "open" to "closed" transformation between G and F forms and its implications on the relative motion of several key residues and the formation of water wires have been characterized in
molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of t ...
and QM/MM simulations.


Assembly dynamics

Actin filaments are often rapidly assembled and disassembled, allowing them to generate force and support cell movement. Assembly classically occurs in three steps. First, the "nucleation phase", in which two to three G-actin molecules slowly join to form a small oligomer that will nucleate further growth. Second, the "elongation phase", when the actin filament rapidly grows by the addition of many actin molecules to both ends. As the filament grows, actin molecules are added to the (+) end of the filament around 10 times faster than to the (−) end, and so filaments tend to primarily grow at the (+) end. Third, the "steady-state phase", where an equillibrium is reached as actin molecules join and leave the filament at the same rate, maintaining the filament's length. While the filament's length remains constant in the steady-state phase, new molecules are constantly being added to the (+) end and falling off the (−) end, a phenomenon called "treadmilling" as a given actin molecule would appear to move along the strand. In isolation, whether a filament will grow or shrink, and how quickly, are determined by the concentration of G-actin around the filament; however, in cells, the dynamics of actin filaments are heavily influenced by various actin-binding proteins.


Actin binding proteins

The actin cytoskeleton ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' is not exclusively composed of actin, other proteins are required for its formation, continuance, and function. These proteins are called actin-binding proteins and they are involved in actin's polymerization, depolymerization, stability, and organisation. The diversity of these proteins is such that actin is thought to be the protein that takes part in the greatest number of protein-protein interactions. The nucleation of new actin filaments – the rate-limiting step in actin polymerization – is aided by actin-nucleating proteins such as formins (like formin-2) and the
Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...
. Formins help to nucleate long actin filaments. They bind two free actin-ATP molecules, bringing them together. Then as the filament begins to grow, formin moves along the (+) end of the growing filament, all the while recruiting actin-binding proteins that promote filament growth, and excluding capping proteins that would block filament extension. Branches in actin filaments are typically nucleated by the
Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...
in concert with nucleation promoting factors. Nucleation promoting factors bind two free G-actin molecules, then recruit and activate the Arp2/3 complex. The activated Arp2/3 complex attaches to an existing actin filament, and uses the two bound G-actin molecules to nucleate a new actin filament branching off of the old one at a 70° angle. As filaments grow, the pool of available G-actin molecules is managed by G-actin-binding proteins such as profilin and thymosin β-4. Profilin ensures a supply of available actin-ATP by binding to ADP-bound G-actin and promoting the exchange of ADP for ATP. Profilin's binding to the actin molecule physically blocks its addition to a filament's (−) end, but permits it to join the (+) end. Once the actin-ATP has joined the filament, profilin releases it. As formins promote the nucleation and extension of new actin filaments, they recruit profilin to the area, increasing the local concentration of actin-ATP to boost filament growth. In contrast, thymosin β-4 binds and sequesters actin-ATP, preventing it from joining a microfilament. Once an actin fiber is established, the dynamics of its growth or collapse are influenced by numerous proteins. Existing strands can be interrupted by filament cleaving proteins, such as
cofilin ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle contractio ...
and gelsolin. Cofilin binds along two actin-ADP molecules in a filament, forcing a movement that destabilizes the filament and causes it to break. Gelsolin inserts itself between actin molecules in a filament, disrupting the filament. After the filament breaks, gelsolin remains attached to the new (+) end, preventing it from growing, thus forcing its disassembly. Other proteins bind to the ends of actin filaments, stabilizing them. These are called "capping proteins" and include CapZ and tropomodulin. CapZ binds the (+) end of a filament, preventing further addition or loss of actin from that end. Tropomodulin binds to a filament's (−) end, again preventing addition or loss of molecule's at that end. Tropomodulin is typically found in cells that require extremely stable actin filaments, such as those in muscle and red blood cells. These actin binding proteins are typically regulated by various cellular signals to control actin assembly dynamics in different cellular locations. Formins, for example, are typically folded in an inactive conformation until they're activated by the binding of the
small GTPase Small GTPases (), also known as small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotr ...
Rho. Actin branching at the cell membrane is important for cell movement, and so the plasma membrane lipid PIP2 activates the nucleation promoting factor
WASp A wasp is any insect of the narrow-waisted suborder Apocrita of the order Hymenoptera which is neither a bee nor an ant; this excludes the broad-waisted sawflies (Symphyta), which look somewhat like wasps, but are in a separate suborder. ...
and inhibits CapZ. WASp is also activated by the small GTPase Cdc42, while another nucleation promoting factor WAVE is activated by the GTPase Rac1.


Genetics

Although most
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
s have only a single actin gene, higher eukaryotes, in general, express several isoforms of actin encoded by a family of related genes. Mammals have at least six actin isoforms coded by separate genes, which are divided into three classes – alpha, beta, and gamma – according to their
isoelectric point The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). However, pI is also u ...
s. In general, alpha actins are found in muscle ( α-skeletal, α-aortic smooth, α-cardiac), whereas beta and gamma isoforms are prominent in non-muscle cells ( β-cytoplasmic, γ1-cytoplasmic, γ2-enteric smooth). Although the amino acid sequences and ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' properties of the isoforms are highly similar, these isoforms cannot completely substitute for one another ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
''. Plants contains more than 60 actin genes and pseudogenes. The typical actin gene has an approximately 100-nucleotide
5' UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of t ...
, a 1200-nucleotide translated region, and a 200-nucleotide
3' UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...
. The majority of actin genes are interrupted by introns, with up to six introns in any of 19 well-characterised locations. The high conservation of the family makes actin the favoured model for studies comparing the introns-early and introns-late models of intron evolution.


Evolution

Actin and closely related proteins are present in all organisms, suggesting the common ancestor of all life on Earth had actin. Actin is one of the most conserved proteins throughout the evolution of eukaryotes. The sequences of actin proteins from animals and
amoeba An amoeba (; less commonly spelled ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudop ...
e are 80% identical despite being separated by approximately one billion years of evolution. Many
unicellular A unicellular organism, also known as a single-celled organism, is an organism that consists of a single cell, unlike a multicellular organism that consists of multiple cells. Organisms fall into two general categories: prokaryotic organisms and ...
eukaryotes have a single actin gene, while multicellular eukaryotes often have several closely related genes that serve specialized functions. Humans have six; plants have 10 or more. In addition to actin, eukaryotes have a large family of actin-related proteins, or "Arps", that share a common ancestor with actin and are called Arp1–Arp11, with Arp1 the most closely related to actin, and Arp11 the least. Bacteria encode three types of actin: MreB influences cell shape, FtsA cell division, and ParM separation of large plasmids. Some archaea have a bacteria-like MreB gene, while others have an actin gene that more closely resembles eukaryote actin. The eukaryotic cytoskeleton of organisms among all taxonomic groups have similar components to actin and tubulin. For example, the protein that is coded by the ''
ACTG2 Actin, gamma-enteric smooth muscle is a protein that in humans is encoded by the ''ACTG2'' gene. Actins are highly conserved proteins that are involved in various types of cell motility, and maintenance of the cytoskeleton. In vertebrates, three ...
'' gene in humans is completely equivalent to the homologues present in rats and mice, even though at a
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
level the similarity decreases to 92%. However, there are major differences with the equivalents in prokaryotes (
FtsZ FtsZ is a protein encoded by the ''ftsZ'' gene that assembles into a ring at the future site of bacterial cell division (also called the Z ring). FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filam ...
and MreB), where the similarity between nucleotide sequences is between 40 and 50 % among different
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
and archaea species. Some authors suggest that the ancestral protein that gave rise to the model eukaryotic actin resembles the proteins present in modern bacterial cytoskeletons. Some authors point out that the behaviour of actin, tubulin, and
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
, a protein involved in the stabilization and regulation of DNA, are similar in their ability to bind nucleotides and in their ability of take advantage of
Brownian motion Brownian motion, or pedesis (from grc, πήδησις "leaping"), is the random motion of particles suspended in a medium (a liquid or a gas). This pattern of motion typically consists of random fluctuations in a particle's position insi ...
. It has also been suggested that they all have a common ancestor. Therefore,
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
ary processes resulted in the diversification of ancestral proteins into the varieties present today, conserving, among others, actins as efficient molecules that were able to tackle essential ancestral biological processes, such as endocytosis. The
Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...
is widely found in all
eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
organisms.


Equivalents in prokaryotes

The bacterial cytoskeleton contains proteins that are highly similar to actin monomers and polymers. The bacterial protein MreB polymerizes into thin non-helical filaments and occasionally into helical structures similar to F-actin. Furthermore, its crystalline structure is very similar to that of G-actin (in terms of its three-dimensional conformation), there are even similarities between the MreB protofilaments and F-actin. The bacterial cytoskeleton also contains the
FtsZ FtsZ is a protein encoded by the ''ftsZ'' gene that assembles into a ring at the future site of bacterial cell division (also called the Z ring). FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filam ...
proteins, which are similar to
tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
. Bacteria therefore possess a cytoskeleton with homologous elements to actin (for example, MreB, AlfA, ParM, FtsA, and MamK), even though the amino acid sequence of these proteins diverges from that present in animal cells. However, such proteins have a high degree of
structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such ...
similarity to eukaryotic actin. The highly dynamic microfilaments formed by the aggregation of MreB and ParM are essential to cell viability and they are involved in cell morphogenesis,
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
segregation, and cell polarity. ParM is an actin homologue that is coded in a plasmid and it is involved in the regulation of plasmid DNA. ParMs from different bacterial plasmids can form astonishingly diverse helical structures comprising two or four strands to maintain faithful plasmid inheritance. In archaea the homologue Ta0583 is even more similar to the eukaryotic actins.


Molecular pathology

The majority of mammals possess six different actin
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s. Of these, two code for the
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
(''
ACTB Beta-actin (human gene and protein abbreviation ''ACTB''/ACTB) is one of six different actin isoforms which have been identified in humans. This is one of the two nonmuscle cytoskeletal actins. Actins are highly conserved proteins that are invol ...
'' and '' ACTG1'') while the other four are involved in
skeletal striated muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
(''
ACTA1 Actin, alpha skeletal muscle is a protein that in humans is encoded by the ''ACTA1'' gene. Actin alpha 1 which is expressed in skeletal muscle is one of six different actin isoforms which have been identified. Actins are highly conserved protei ...
''),
smooth muscle tissue Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...
(''
ACTA2 ACTA2 (actin alpha 2) is an actin protein with several aliases including alpha-actin, alpha-actin-2, aortic smooth muscle or alpha smooth muscle actin (α-SMA, SMactin, alpha-SM-actin, ASMA). Actins are a family of globular multi-functional pr ...
''),
intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
muscles (''
ACTG2 Actin, gamma-enteric smooth muscle is a protein that in humans is encoded by the ''ACTG2'' gene. Actins are highly conserved proteins that are involved in various types of cell motility, and maintenance of the cytoskeleton. In vertebrates, three ...
'') and
cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
('' ACTC1''). The actin in the cytoskeleton is involved in the pathogenic mechanisms of many
infectious agents In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
, including
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
. The vast majority of the mutations that affect actin are point mutations that have a dominant effect, with the exception of six mutations involved in
nemaline myopathy Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ...
. This is because in many cases the mutant of the actin monomer acts as a “cap” by preventing the elongation of F-actin.


Pathology associated with ''ACTA1''

''
ACTA1 Actin, alpha skeletal muscle is a protein that in humans is encoded by the ''ACTA1'' gene. Actin alpha 1 which is expressed in skeletal muscle is one of six different actin isoforms which have been identified. Actins are highly conserved protei ...
'' is the gene that codes for the α- isoform of actin that is predominant in human
skeletal striated muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
s, although it is also expressed in heart muscle and in the thyroid gland. Its DNA sequence consists of seven exons that produce five known transcripts. The majority of these consist of point mutations causing substitution of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s. The mutations are in many cases associated with a
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
that determines the severity and the course of the affliction. The mutation alters the structure and function of skeletal muscles producing one of three forms of myopathy: type 3
nemaline myopathy Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ...
, congenital myopathy with an excess of thin myofilaments (CM) and congenital myopathy with fibre type disproportion (CMFTD). Mutations have also been found that produce core myopathies. Although their phenotypes are similar, in addition to typical nemaline myopathy some specialists distinguish another type of myopathy called actinic nemaline myopathy. In the former, clumps of actin form instead of the typical rods. It is important to state that a patient can show more than one of these
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
s in a
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
. The most common symptoms consist of a typical facial morphology (myopathic facies), muscular weakness, a delay in motor development and respiratory difficulties. The course of the illness, its gravity, and the age at which it appears are all variable and overlapping forms of myopathy are also found. A symptom of nemaline myopathy is that "nemaline rods" appear in differing places in type 1 muscle fibres. These rods are non-
pathognomonic Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...
structures that have a similar composition to the Z disks found in the
sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...
. The
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of this myopathy is very varied. Many mutations occur in the region of actin's indentation near to its
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
binding sites, while others occur in Domain 2, or in the areas where interaction occurs with associated proteins. This goes some way to explain the great variety of clumps that form in these cases, such as Nemaline or Intranuclear Bodies or Zebra Bodies. Changes in actin's folding occur in nemaline myopathy as well as changes in its aggregation and there are also changes in the
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of other associated proteins. In some variants where intranuclear bodies are found the changes in the folding masks the nucleus's protein exportation signal so that the accumulation of actin's mutated form occurs in the cell nucleus. On the other hand, it appears that mutations to ''ACTA1'' that give rise to a CFTDM have a greater effect on sarcomeric function than on its structure. Recent investigations have tried to understand this apparent paradox, which suggests there is no clear correlation between the number of rods and muscular weakness. It appears that some mutations are able to induce a greater apoptosis rate in type II muscular fibres.


In smooth muscle

There are two isoforms that code for actins in the
smooth muscle tissue Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...
: ''
ACTG2 Actin, gamma-enteric smooth muscle is a protein that in humans is encoded by the ''ACTG2'' gene. Actins are highly conserved proteins that are involved in various types of cell motility, and maintenance of the cytoskeleton. In vertebrates, three ...
'' codes for the largest actin isoform, which has nine exons, one of which, the one located at the 5' end, is not translated. It is a γ-actin that is expressed in the enteric smooth muscle. No mutations to this gene have been found that correspond to pathologies, although
microarrays A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon ...
have shown that this protein is more often expressed in cases that are resistant to
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
using
cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...
. ''
ACTA2 ACTA2 (actin alpha 2) is an actin protein with several aliases including alpha-actin, alpha-actin-2, aortic smooth muscle or alpha smooth muscle actin (α-SMA, SMactin, alpha-SM-actin, ASMA). Actins are a family of globular multi-functional pr ...
'' codes for an α-actin located in the smooth muscle, and also in vascular smooth muscle. It has been noted that the MYH11 mutation could be responsible for at least 14% of hereditary thoracic aortic aneurisms particularly Type 6. This is because the mutated variant produces an incorrect filamentary assembly and a reduced capacity for vascular smooth muscle contraction. Degradation of the aortic media has been recorded in these individuals, with areas of disorganization and hyperplasia as well as stenosis of the aorta's
vasa vasorum Vasa vasorum are small blood vessels that comprise a vascular network supplying the walls of large blood vessels, such as elastic arteries (e.g., the aorta) and large veins (e.g., the venae cavae). The name derives . Occasionally two differen ...
. The number of afflictions that the gene is implicated in is increasing. It has been related to Moyamoya disease and it seems likely that certain mutations in heterozygosis could confer a predisposition to many vascular pathologies, such as thoracic aortic aneurysm and
ischaemic heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
. The α-actin found in smooth muscles is also an interesting marker for evaluating the progress of liver
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
.


In heart muscle

The '' ACTC1'' gene codes for the α-actin isoform present in heart muscle. It was first sequenced by Hamada and co-workers in 1982, when it was found that it is interrupted by five introns. It was the first of the six genes where alleles were found that were implicated in pathological processes. A number of structural disorders associated with point mutations of this gene have been described that cause malfunctioning of the heart, such as Type 1R
dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...
and Type 11 hypertrophic cardiomyopathy. Certain defects of the
atrial septum The interatrial septum is the wall of tissue that separates the right and left atria of the heart. Structure The interatrial septum is a that lies between the left atrium and right atrium of the human heart. The interatrial septum lies at angl ...
have been described recently that could also be related to these mutations. Two cases of dilated cardiomyopathy have been studied involving a substitution of highly conserved
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s belonging to the protein domains that bind and intersperse with the Z discs. This has led to the theory that the dilation is produced by a defect in the transmission of contractile force in the
myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a mus ...
s. The mutations in ACTC1 are responsible for at least 5% of hypertrophic cardiomyopathies. The existence of a number of point mutations have also been found: * Mutation E101K: changes of net charge and formation of a weak electrostatic link in the actomyosin-binding site. * P166A: interaction zone between actin monomers. * A333P: actin-myosin interaction zone. Pathogenesis appears to involve a compensatory mechanism: the mutated proteins act like toxins with a dominant effect, decreasing the heart's ability to
contract A contract is a legally enforceable agreement between two or more parties that creates, defines, and governs mutual rights and obligations between them. A contract typically involves the transfer of goods, services, money, or a promise to tr ...
causing abnormal mechanical behaviour such that the hypertrophy, that is usually delayed, is a consequence of the cardiac muscle's normal response to
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
. Recent studies have discovered ACTC1 mutations that are implicated in two other pathological processes: Infantile idiopathic restrictive cardiomyopathy, and noncompaction of the left ventricular myocardium.


In cytoplasmatic actins

''
ACTB Beta-actin (human gene and protein abbreviation ''ACTB''/ACTB) is one of six different actin isoforms which have been identified in humans. This is one of the two nonmuscle cytoskeletal actins. Actins are highly conserved proteins that are invol ...
'' is a highly complex
locus Locus (plural loci) is Latin for "place". It may refer to: Entertainment * Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front * ''Locus'' (magazine), science fiction and fantasy magazine ** ''Locus Award' ...
. A number of pseudogenes exist that are distributed throughout the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
, and its sequence contains six exons that can give rise to up to 21 different transcriptions by alternative splicing, which are known as the β-actins. Consistent with this complexity, its products are also found in a number of locations and they form part of a wide variety of processes (
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
, NuA4
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
-acyltransferase complex, cell nucleus) and in addition they are associated with the mechanisms of a great number of pathological processes (
carcinomas Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...
, juvenile dystonia, infection mechanisms,
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...
malformations and tumour invasion, among others). A new form of actin has been discovered, kappa actin, which appears to substitute for β-actin in processes relating to tumours. Three pathological processes have so far been discovered that are caused by a direct alteration in gene sequence: * Hemangiopericytoma with t(7;12)(p22;q13)-translocations is a rare affliction, in which a translocational mutation causes the fusion of the ''ACTB'' gene over
GLI1 Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells. Function The Gli proteins are the effectors of Hedgehog (Hh) ...
in
Chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...
. * Juvenile onset dystonia is a rare degenerative disease that affects the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
; in particular, it affects areas of the neocortex and
thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
, where rod-like
eosinophilic Eosinophilic (Greek suffix -phil-, meaning ''loves eosin'') is the staining of tissues, cells, or organelles after they have been washed with eosin, a dye. Eosin is an acidic dye for staining cell cytoplasm, collagen, and muscle fibers. ''E ...
inclusions are formed. The affected individuals represent a
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
with deformities on the median line, sensory hearing loss and dystonia. It is caused by a point mutation in which the amino acid tryptophan replaces arginine in position 183. This alters actin's interaction with the ADF/
cofilin ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle contractio ...
system, which regulates the dynamics of
nerve cell A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...
cytoskeleton formation. * A dominant point mutation has also been discovered that causes neutrophil granulocyte dysfunction and recurring
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
s. It appears that the mutation modifies the domain responsible for binding between profilin and other regulatory proteins. Actin's affinity for profilin is greatly reduced in this allele. The '' ACTG1'' locus codes for the cytosolic γ-actin protein that is responsible for the formation of cytoskeletal microfilaments. It contains six exons, giving rise to 22 different mRNAs, which produce four complete isoforms whose form of expression is probably dependent on the type of tissue they are found in. It also has two different DNA promoters. It has been noted that the sequences translated from this locus and from that of β-actin are very similar to the predicted ones, suggesting a common ancestral sequence that suffered duplication and genetic conversion. In terms of pathology, it has been associated with processes such as amyloidosis,
retinitis pigmentosa Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...
, infection mechanisms,
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
diseases, and various types of congenital hearing loss. Six autosomal-dominant point mutations in the sequence have been found to cause various types of hearing loss, particularly sensorineural hearing loss linked to the DFNA 20/26 locus. It seems that they affect the
stereocilia Stereocilia (or stereovilli or villi) are non-motile apical cell modifications. They are distinct from cilia and microvilli, but are closely related to microvilli. They form single "finger-like" projections that may be branched, with normal cell ...
of the ciliated cells present in the inner ear's Organ of Corti. β-actin is the most abundant protein found in human tissue, but it is not very abundant in ciliated cells, which explains the location of the pathology. On the other hand, it appears that the majority of these mutations affect the areas involved in linking with other proteins, particularly actomyosin. Some experiments have suggested that the pathological mechanism for this type of hearing loss relates to the F-actin in the mutations being more sensitive to cofilin than normal. However, although there is no record of any case, it is known that γ-actin is also expressed in skeletal muscles, and although it is present in small quantities, model organisms have shown that its absence can give rise to myopathies.


Other pathological mechanisms

Some infectious agents use actin, especially cytoplasmic actin, in their
life cycle Life cycle, life-cycle, or lifecycle may refer to: Science and academia *Biological life cycle, the sequence of life stages that an organism undergoes from birth to reproduction ending with the production of the offspring * Life-cycle hypothesis ...
. Two basic forms are present in
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
: * ''
Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host ...
'', some species of '' Rickettsia'', '' Shigella flexneri'' and other intracellular germs escape from
phagocytic Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is c ...
vacuoles by coating themselves with a capsule of actin filaments. ''L. monocytogenes'' and ''S. flexneri'' both generate a tail in the form of a "comet tail" that gives them mobility. Each species exhibits small differences in the molecular polymerization mechanism of their "comet tails". Different displacement velocities have been observed, for example, with ''Listeria'' and ''Shigella'' found to be the fastest. Many experiments have demonstrated this mechanism ''in vitro''. This indicates that the bacteria are not using a myosin-like protein motor, and it appears that their propulsion is acquired from the pressure exerted by the polymerization that takes place near to the microorganism's cell wall. The bacteria have previously been surrounded by ABPs from the host, and as a minimum the covering contains
Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...
, Ena/VASP proteins, cofilin, a buffering protein and nucleation promoters, such as
vinculin In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cel ...
complex. Through these movements they form protrusions that reach the neighbouring cells, infecting them as well so that the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
can only fight the infection through cell immunity. The movement could be caused by the modification of the curve and debranching of the filaments. Other species, such as ''
Mycobacterium marinum ''Mycobacterium marinum'' is a slow growing mycobacterium (SGM) belonging to the genus ''Mycobacterium'' and the phylum Actinobacteria. The strain marinum was first identified by Aronson in 1926 and it is observed as a pathogenic mycobacterium. F ...
'' and ''
Burkholderia pseudomallei ''Burkholderia pseudomallei'' (also known as ''Pseudomonas pseudomallei'') is a Gram-negative, bipolar, aerobic, motile rod-shaped bacterium. It is a soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in T ...
'', are also capable of localized polymerization of cellular actin to aid their movement through a mechanism that is centered on the Arp2/3 complex. In addition the vaccine
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
'' Vaccinia'' also uses elements of the actin cytoskeleton for its dissemination. * '' Pseudomonas aeruginosa'' is able to form a protective
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
in order to escape a
host organism In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
’s defences, especially white blood cells and
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
. The biofilm is constructed using DNA and actin filaments from the host organism. In addition to the previously cited example, actin polymerization is stimulated in the initial steps of the internalization of some viruses, notably
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
, by, for example, inactivating the cofilin complex. The role that actin plays in the invasion process of cancer cells has still not been determined.


Applications

Actin is used in scientific and technological laboratories as a track for molecular motors such as myosin (either in muscle tissue or outside it) and as a necessary component for cellular functioning. It can also be used as a diagnostic tool, as several of its anomalous variants are related to the appearance of specific pathologies. * Nanotechnology. Actin-myosin systems act as molecular motors that permit the transport of vesicles and organelles throughout the cytoplasm. It is possible that actin could be applied to nanotechnology as its dynamic ability has been harnessed in a number of experiments including those carried out in acellular systems. The underlying idea is to use the microfilaments as tracks to guide molecular motors that can transport a given load. That is actin could be used to define a circuit along which a load can be transported in a more or less controlled and directed manner. In terms of general applications, it could be used for the directed transport of molecules for deposit in determined locations, which would permit the controlled assembly of nanostructures. These attributes could be applied to laboratory processes such as on ''
lab-on-a-chip A lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single integrated circuit (commonly called a "chip") of only millimeters to a few square centimeters to achieve automation and high-throughput screening. ...
'', in nanocomponent mechanics and in nanotransformers that convert mechanical energy into electrical energy. *Actin is used as an internal control in
western blot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
s to ascertain that equal amounts of protein have been loaded on each lane of the gel. In the blot example shown on the left side, 75 µg of total protein was loaded in each well. The blot was reacted with anti-β-actin antibody (for other details of the blot see the reference ) The use of actin as an internal control is based on the assumption that its expression is practically constant and independent of experimental conditions. By comparing the expression of the gene of interest to that of the actin, it is possible to obtain a relative quantity that can be compared between different experiments, whenever the expression of the latter is constant. It is worth pointing out that actin does not always have the desired stability in its gene expression. *Health. Some
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
s of actin cause diseases; for this reason techniques for their detection have been developed. In addition, actin can be used as an indirect marker in surgical pathology: it is possible to use variations in the pattern of its distribution in tissue as a marker of invasion in
neoplasia A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, vasculitis, and other conditions. Further, due to actin's close association with the apparatus of muscular contraction its levels in skeletal muscle diminishes when these tissues atrophy, it can therefore be used as a marker of this physiological process. * Food technology. It is possible to determine the quality of certain processed foods, such as
sausages A sausage is a type of meat product usually made from ground meat—often pork, beef, or poultry—along with salt, spices and other flavourings. Other ingredients, such as grains or breadcrumbs may be included as fillers or extenders. W ...
, by quantifying the amount of actin present in the constituent meat. Traditionally, a method has been used that is based on the detection of 3-methylhistidine in hydrolyzed samples of these products, as this compound is present in actin and F-myosin's heavy chain (both are major components of muscle). The generation of this compound in flesh derives from the methylation of
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...
residues present in both proteins.


History

Actin was first observed
experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into Causality, cause-and-effect by demonstrating what outcome oc ...
ally in 1887 by W.D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin that he called "myosin-ferment". However, Halliburton was unable to further refine his findings, and the discovery of actin is credited instead to
Brunó Ferenc Straub Brunó Ferenc Straub (5 January 1914 in Nagyvárad, Austria-Hungary (now Oradea, Romania) – 15 February 1996) was a biochemist. As a young scholar he was a research assistant of Albert Szent-Györgyi at the University of Szeged, and subsequ ...
, a young biochemist working in
Albert Szent-Györgyi Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...
's laboratory at the Institute of Medical Chemistry at the
University of Szeged , mottoeng = Truth. Bravery. Freedom. , established = , type = Public research university , founder = Emperor Franz Joseph I , affiliation = European University Association, Science Without Borders, Confucius Institute , budget = US$220 m ...
,
Hungary Hungary ( hu, Magyarország ) is a landlocked country in Central Europe. Spanning of the Pannonian Basin, Carpathian Basin, it is bordered by Slovakia to the north, Ukraine to the northeast, Romania to the east and southeast, Serbia to the ...
. Following up on the discovery of Ilona Banga & Szent-Györgyi in 1941 that the coagulation only occurs in some myosin extractions and was reversed upon the addition of ATP, Straub identified and purified actin from those myosin preparations that did coagulate. Building on Banga's original extraction method, he developed a novel technique for extracting muscle protein that allowed him to isolate substantial amounts of relatively
pure Pure may refer to: Computing * A pure function * A pure virtual function * PureSystems, a family of computer systems introduced by IBM in 2012 * Pure Software, a company founded in 1991 by Reed Hastings to support the Purify tool * Pure-FTPd, F ...
actin, published in 1942. Straub's method is essentially the same as that used in laboratories today. Since Straub's protein was necessary to activate the coagulation of myosin, it was dubbed ''actin''. Realizing that Banga's coagulating myosin preparations contained actin as well, Szent-Györgyi called the mixture of both proteins
actomyosin Myofilaments are the three protein filaments of myofibrils in muscle cells. The main proteins involved are myosin, actin, and titin. Myosin and actin are the ''contractile proteins'' and titin is an elastic protein. The myofilaments act toget ...
. The hostilities of
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...
meant Szent-Gyorgyi was unable to publish his lab's work in
Western Western may refer to: Places *Western, Nebraska, a village in the US *Western, New York, a town in the US *Western Creek, Tasmania, a locality in Australia *Western Junction, Tasmania, a locality in Australia *Western world, countries that id ...
scientific journals. Actin therefore only became well known in the West in 1945, when their paper was published as a supplement to the ''Acta Physiologica Scandinavica''. Straub continued to work on actin, and in 1950 reported that actin contains bound ATP and that, during
polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
ization of the protein into microfilaments, the
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
is hydrolyzed to ADP and inorganic
phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...
(which remain bound to the microfilament). Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. In fact, this is true only in smooth muscle, and was not supported through experimentation until 2001. The amino acid sequencing of actin was completed by M. Elzinga and co-workers in 1973. The
crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric patterns ...
of G-actin was solved in 1990 by Kabsch and colleagues. In the same year, a model for F-actin was proposed by Holmes and colleagues following experiments using co-crystallization with different proteins. The procedure of co-crystallization with different proteins was used repeatedly during the following years, until in 2001 the isolated protein was crystallized along with ADP. However, there is still no high-resolution X-ray structure of F-actin. The crystallization of G-actin was possible due to the use of a
rhodamine Rhodamine is a family of related dyes, a subset of the triarylmethane dyes. They are derivatives of xanthene. Important members of the rhodamine family are Rhodamine 6G, Rhodamine 123, and Rhodamine B. They are mainly used to dye paper and inks ...
conjugate that impedes polymerization by blocking the amino acid cys-374.; Christine Oriol-Audit died in the same year that actin was first crystallized but she was the researcher that in 1977 first crystallized actin in the absence of Actin Binding Proteins (ABPs). However, the resulting crystals were too small for the available technology of the time. Although no high-resolution model of actin's filamentous form currently exists, in 2008 Sawaya's team were able to produce a more exact model of its structure based on multiple crystals of actin dimers that bind in different places. This model has subsequently been further refined by Sawaya and Lorenz. Other approaches such as the use of cryo-electron microscopy and synchrotron radiation have recently allowed increasing resolution and better understanding of the nature of the interactions and conformational changes implicated in the formation of actin filaments.


Research


Chemical inhibitors

A number of natural
toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...
s that interfere with actin's dynamics are widely used in research to study actin's role in biology.
Latrunculin The latrunculins are a family of natural products and toxins produced by certain sponges, including genus '' Latrunculia'' and ''Negombata'', whence the name is derived. It binds actin monomers near the nucleotide binding cleft with 1:1 stoichiome ...
– a toxin produced by
sponge Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate throug ...
s – binds to G-actin preventing it from joining microfilaments. Cytochalasin D – produced by certain
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
– serves as a capping factor, binding to the (+) end of a filament and preventing further addition of actin molecules. In contrast, the sponge toxin jasplakinolide promotes the nucleation of new actin filaments by binding and stabilzing pairs of actin molecules.
Phalloidin Phalloidin belongs to a class of toxins called phallotoxins, which are found in the death cap mushroom ''(Amanita phalloides)''. It is a rigid bicyclic heptapeptide that is lethal after a few days when injected into the bloodstream. The major sy ...
– from the "death cap" mushroom '' Amanita phalloides'' – binds to adjacent actin molecules within the F-actin filament, stabilizing the filament and preventing its depolymerization. Phalloidin is often labelled with
fluorescent dyes A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with sev ...
to visualize actin filaments by
fluorescence microscopy A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microscop ...
.


See also

* Actin remodeling — effect on cell structure and shape * Active matter * Filopodia * Intermediate filament *
Lamellipodium The lamellipodium (plural lamellipodia) (from Latin ''lamella'', related to ', "thin sheet", and the Greek radical ''pod-'', "foot") is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional ...
* Motor protein — converts chemical energy into mechanical work *
Neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
* Phallotoxin


References


Works cited

* *


External links


Actin Staining Techniques (Live and Fixed Cell Staining)
* * *
3D macromolecular structures of actin filaments from the EM Data Bank(EMDB)
{{Authority control Autoantigens Cytoskeleton proteins Articles containing video clips