Septins are a group of
GTP-
binding protein A binding protein is any protein that acts as an agent to bind two or more molecules together.
Examples include:
*DNA-binding protein
**Single-strand binding protein
**Telomere-binding protein
*RNA-binding protein
**Poly(A)-binding protein
** Nuc ...
s
expressed in all
eukaryotic cells
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 ...
except
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
s.
Different septins form
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein c ...
es with each other. These complexes can further assemble into filaments, rings and gauzes. Assembled as such, septins function in cells by localizing other
proteins
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, respo ...
, either by providing a scaffold to which proteins can attach, or by forming a barrier preventing the
diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
of molecules from one compartment of the cell to another,
or in the
cell cortex
The cell cortex, also known as the actin cortex, cortical cytoskeleton or actomyosin cortex, is a specialized layer of cytoplasmic proteins on the inner face of the cell membrane. It functions as a modulator of membrane behavior and cell surface p ...
as a barrier to the diffusion of membrane-bound proteins.
Septins have been implicated in the localization of cellular processes at the site of
cell division
Cell division is the process by which a parent cell (biology), 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 eukar ...
, and at 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 ( ...
at sites where specialized structures like
cilia
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
or
flagella
A flagellum (; ) is a hairlike appendage that protrudes from certain plant and animal sperm cells, and from a wide range of microorganisms to provide motility. Many protists with flagella are termed as flagellates.
A microorganism may have f ...
are attached to the cell body.
In yeast cells, they compartmentalize parts of the cell and build scaffolding to provide structural support during cell division at the
septum
In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate.
Examples
Human anatomy
* Interatri ...
, from which they derive their name.
Research in human cells suggests that septins build cages around
pathogenic bacteria
Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often Probiotic, beneficial but others can cause infectious diseases. The n ...
, that immobilize and prevent them from invading other cells.
As filament forming proteins, septins can be considered part 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 compos ...
.
Apart from forming non-polar filaments, septins associate with
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 ( ...
s, the cell cortex,
actin filament
Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pro ...
s and
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
s.
Structure
![Septin assembly](https://upload.wikimedia.org/wikipedia/commons/d/d9/Septin_assembly.png)
Septins are
P-Loop
The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982.
Of the two motifs, the A motif is t ...
-NTPase
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, respo ...
s that range in weight from 30-65 kDa. Septins are highly conserved between different eukaryotic species. They are composed of a variable-length proline rich
N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
with a
basic
BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Thomas E. Kurtz at Dartmouth College ...
phosphoinositide
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
binding motif important for membrane association, a
GTP-binding domain, a highly conserved Septin Unique Element domain, and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
extension including a
coiled coil
A coiled coil is a structural motif in proteins in which 2–7
alpha-helices are coiled together like the strands of a rope. (Dimers and trimers are the most common types.) Many coiled coil-type proteins are involved in important biological fun ...
domain of varying length.
Septins interact either via their respective GTP-binding domains, or via both their N- and C-termini. Different organisms express a different number of septins, and from those symmetric oligomers are formed. For example, in yeast the octameric complex formed is Cdc11-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11. In humans, hexameric or octameric complexes are possible. Initially, it was indicated that the human complex was Sept7-Sept6-Sept2-Sept2-Sept6-Sept7; but recently this order has been revised to Sept2-Sept6-Sept7-Sept7-Sept6-Sept2 (or Sept2-Sept6-Sept7-Sept3-Sept3-Sept7-Sept6-Sept2
in case of octameric hetero-oligomers). These complexes then associate to form non-polar filaments, filament bundles, cages or ring structures in cells.
Occurrence
Septins are found in
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 ...
,
animals
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
, and some eukaryotic
algae
Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...
but are not found in plants.
In yeast
There are seven different septins in ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
''. Five of those are involved in mitosis, while two (Spr3 and Spr28) are specific to
sporulation
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
.
Mitotic septins (Cdc3, Cdc10, Cdc11, Cdc12, Shs1) form a ring structure at the bud neck during
cell division
Cell division is the process by which a parent cell (biology), 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 eukar ...
.
They are involved in the selection of the bud-site, the positioning of the
mitotic spindle
In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...
, polarized growth, and
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
. The sporulating septins (Spr3, Spr28) localize together with Cdc3 and Cdc11 to the edges of prospore membranes.
Organization
Septins form a specialised region in the cell cortex known as the septin cortex.
The septin cortex undergoes several changes throughout 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 subs ...
: The first visible septin structure is a distinct ring which appears ~15 min before
bud
In botany, a bud is an undeveloped or embryonic shoot and normally occurs in the axil of a leaf or at the tip of a stem. Once formed, a bud may remain for some time in a dormant condition, or it may form a shoot immediately. Buds may be spec ...
emergence. After
bud
In botany, a bud is an undeveloped or embryonic shoot and normally occurs in the axil of a leaf or at the tip of a stem. Once formed, a bud may remain for some time in a dormant condition, or it may form a shoot immediately. Buds may be spec ...
emergence, the ring broadens to assume the shape of an
hourglass
An hourglass (or sandglass, sand timer, sand clock or egg timer) is a device used to measure the passage of time. It comprises two glass bulbs connected vertically by a narrow neck that allows a regulated flow of a substance (historically sand) ...
around the mother-bud neck. During
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
, the septin cortex splits into a double ring which eventually disappears. How can the septin cortex undergo such dramatic changes, although some of its functions may require it to be a stable structure?
FRAP analysis has revealed that the turnover of septins at the neck undergoes multiple changes during 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 subs ...
. The predominant, functional conformation is characterized by a low turnover rate (frozen state), during which the septins are
phosphorylated
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
. Structural changes require a destabilization of the septin cortex (fluid state) induced by
dephosphorylation
In biochemistry, dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deac ...
prior to
bud
In botany, a bud is an undeveloped or embryonic shoot and normally occurs in the axil of a leaf or at the tip of a stem. Once formed, a bud may remain for some time in a dormant condition, or it may form a shoot immediately. Buds may be spec ...
emergence, ring splitting and
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
separation.
The composition of the septin cortex does not only vary throughout 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 subs ...
but also along the mother-bud axis. This polarity of the septin network allows concentration of some
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, respo ...
s primarily to the mother side of the neck, some to the center and others to the
bud
In botany, a bud is an undeveloped or embryonic shoot and normally occurs in the axil of a leaf or at the tip of a stem. Once formed, a bud may remain for some time in a dormant condition, or it may form a shoot immediately. Buds may be spec ...
site.
Functions
Scaffold
The septins act as a scaffold, recruiting many
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, respo ...
s. These protein complexes are involved in
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
,
chitin
Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
deposition,
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
polarity,
spore
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
formation, in the
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 devel ...
checkpoint,
spindle
Spindle may refer to:
Textiles and manufacturing
* Spindle (textiles), a straight spike to spin fibers into yarn
* Spindle (tool), a rotating axis of a machine tool
Biology
* Common spindle and other species of shrubs and trees in genus ''Euony ...
alignment
checkpoint and bud site selection.
Cytokinesis
Budding yeast
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
is driven through two septin dependent, redundant processes: recruitment and contraction of the
actomyosin 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): ...
and formation of the
septum
In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate.
Examples
Human anatomy
* Interatri ...
by
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
fusion with the
plasma 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 (t ...
. In contrast to septin
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s, disruption of one single pathway only leads to a delay in
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
, not complete failure of
cell division
Cell division is the process by which a parent cell (biology), 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 eukar ...
. Hence, the septins are predicted to act at the most upstream level of
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
.
Cell polarity
After the
isotropic
Isotropy is uniformity in all orientations; it is derived . Precise definitions depend on the subject area. Exceptions, or inequalities, are frequently indicated by the prefix ' or ', hence ''anisotropy''. ''Anisotropy'' is also used to describe ...
-
apical
Apical means "pertaining to an apex". It may refer to:
*Apical ancestor, refers to the last common ancestor of an entire group, such as a species (biology) or a clan (anthropology)
*Apical (anatomy), an anatomical term of location for features loc ...
switch in
budding yeast
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
,
cortical components, supposedly of the
exocyst The exocyst is an octameric protein complex involved in vesicle trafficking, specifically the tethering and spatial targeting of post- Golgi vesicles to the plasma membrane prior to vesicle fusion. It is implicated in a number of cell processes, inc ...
and
polarisome, are delocalized from the apical pole to the entire
plasma 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 (t ...
of the bud, but not the mother cell. The septin ring at the neck serves as a cortical barrier that prevents membrane
diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
of these factors between the two compartments. This asymmetric distribution is abolished in septin
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s.
Some conditional septin
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s do not form
bud
In botany, a bud is an undeveloped or embryonic shoot and normally occurs in the axil of a leaf or at the tip of a stem. Once formed, a bud may remain for some time in a dormant condition, or it may form a shoot immediately. Buds may be spec ...
s at their normal axial location. Moreover, the typical localization of some bud-site-selection factors in a double ring at the neck is lost or disturbed in these
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s. This indicates that the septins may serve as anchoring site for such factors in axially
budding
Budding or blastogenesis is a type of asexual reproduction in which a new organism develops from an outgrowth or bud due to cell division at one particular site. For example, the small bulb-like projection coming out from the yeast cell is know ...
cells.
In filamentous fungi
Since their discovery in ''
S. cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have bee ...
,'' septin
homologues have been found in other
eukaryotic
Eukaryotes () are organisms whose cells have a 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 three domains of life. Bacte ...
species, including
filamentous
The word filament, which is descended from Latin ''filum'' meaning " thread", is used in English for a variety of thread-like structures, including:
Astronomy
* Galaxy filament, the largest known cosmic structures in the universe
* Solar filament ...
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 ...
. Septins in filamentous fungi display a variety of different shapes within single
cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
, where they control aspects of filamentous
morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
*Morphology (archaeology), study of the shapes or forms of artifacts
*Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies, ...
.
''Candida albicans''
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 ge ...
of ''
C. albicans'' encodes
homologues to all ''
S. cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have bee ...
'' septins. Without Cdc3 and Cdc12 genes ''Candida albicans'' cannot proliferate, other septins affect morphology and
chitin
Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
deposition, but are not essential. ''Candida albicans'' can display different morphologies of vegetative growth, which determines the appearance of septin structures. Newly forming
hyphae
A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium.
Structure
A hypha consists of one or ...
form a septin ring at the base, Double rings form at sites of hyphal septation, and a septin cap forms at hyphal tips. Elongated septin-
filament
The word filament, which is descended from Latin ''filum'' meaning " thread", is used in English for a variety of thread-like structures, including:
Astronomy
* Galaxy filament, the largest known cosmic structures in the universe
* Solar filament ...
s encircle the spherical
chlamydospore
A chlamydospore is the thick-walled large resting spore of several kinds of fungi, including Ascomycota such as '' Candida'', Basidiomycota such as ''Panus'', and various Mortierellales species. It is the life-stage which survives in unfavourable c ...
s. Double rings of septins at the septation site also bear growth polarity, with the growing tip ring disassembling, while the basal ring remaining intact.
''Aspergillus nidulans''
Five septins are found in ''
A. nidulans'' (AnAspAp, AnAspBp, AnAspCp, AnAspDp, AnAspEp). AnAspBp forms single rings at septation sites that eventually split into double rings. Additionally, AnAspBp forms a ring at sites of branch emergence which broadens into a band as the branch grows. Like in ''
C. albicans,'' double rings reflect polarity of the
hypha
A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium.
Structure
A hypha consists of one or ...
. In the case of ''Aspergillus nidulans'' polarity is conveyed by disassembly of the more basal ring (the ring further away from the hyphal growth tip), leaving the apical ring intact, potentially as a growth guidance cue.
''Ashbya gossypii''
The ''
ascomycete
Ascomycota is a phylum of the kingdom Fungi that, together with the Basidiomycota, forms the subkingdom Dikarya. Its members are commonly known as the sac fungi or ascomycetes. It is the largest phylum of Fungi, with over 64,000 species. The defi ...
A. gossypii'' possesses
homologues to all ''
S. cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have bee ...
'' septins, with one being duplicated (''AgCDC3, AgCDC10, AgCDC11A, AgCDC11B, AgCDC12, AgSEP7''). ''
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 ...
'' studies of AgSep7p-
GFP GFP may refer to:
Organisations
* Gaelic Football Provence, a French Gaelic Athletic Association club
* Geheime Feldpolizei, the German secret military police during the Second World War
* French Group for the Study of Polymers and their Applicat ...
have revealed that septins assemble into discontinuous
hyphal
A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium.
Structure
A hypha consists of one or ...
rings close to growing tips and sites of branch formation,
and into
asymmetric structures at the base of branching points. Rings are made of
filament
The word filament, which is descended from Latin ''filum'' meaning " thread", is used in English for a variety of thread-like structures, including:
Astronomy
* Galaxy filament, the largest known cosmic structures in the universe
* Solar filament ...
s which are long and diffuse close to growing tips and short and compact further away from the tip. During
septum
In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate.
Examples
Human anatomy
* Interatri ...
formation, the
septin ring splits into two to form a double ring. ''Agcdc3Δ, Agcdc10Δ ''and ''Agcdc12Δ ''deletion
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s display aberrant
morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
*Morphology (archaeology), study of the shapes or forms of artifacts
*Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies, ...
and are defective for
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, 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 ...
-ring formation,
chitin
Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
-ring formation, and
sporulation
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
. Due to the lack of
septa
The Southeastern Pennsylvania Transportation Authority (SEPTA) is a regional public transportation authority that operates bus, rapid transit, commuter rail, light rail, and electric trolleybus services for nearly 4 million people in five coun ...
, septin deletion
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s are highly sensitive, and damage of a single
hypha
A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium.
Structure
A hypha consists of one or ...
can result in complete
lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
of a young
mycelium
Mycelium (plural mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Fungal colonies composed of mycelium are found in and on soil and many other substrate (biology), substrates. A typical single ...
.
In animals
In contrast to septins 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 constitut ...
, and in contrast to other
cytoskeletal
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 compo ...
components of animals, septins do not form a continuous network in cells, but several dispersed ones in 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. The ...
of the
cell cortex
The cell cortex, also known as the actin cortex, cortical cytoskeleton or actomyosin cortex, is a specialized layer of cytoplasmic proteins on the inner face of the cell membrane. It functions as a modulator of membrane behavior and cell surface p ...
. These are integrated with
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, 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 ...
bundles and
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
. For example, the actin bundling protein anillin is required for correct spatial control of septin organization.
In the
sperm cells of
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s, septins form a stable ring called annulus in the tail. In mice (and potentially in humans, too), defective annulus formation leads to male infertility.
Human
In humans, septins are involved in
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
,
cilium
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
formation and
neurogenesis
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...
through the capability to recruit other proteins or serve as a diffusion barrier. There are 13 different human genes coding for septins. The septin proteins produced by these genes are grouped into four subfamilies each named after its founding member: (i)
SEPT2
Septin 2, also known as SEPT2, is a protein which in humans is encoded by the ''SEPT2'' gene.
Function
SEPT2 can hetero-oligomerize with SEPT6 and SEPT7 to form filaments. SEPT2 interacted with SEPT6 through its C-terminus, C-terminal coiled-co ...
(
SEPT1
Septin-1 is a protein that in humans is encoded by the ''SEPTIN1'' gene.
It was renamed from SEPT1 to avoid problems where Microsoft Excel would auto-correct the gene name to the date September 1.
Function
This gene is a member of the septin f ...
,
SEPT4
Septin-4 is a protein that in humans is encoded by the ''SEPT4'' gene.
Function
This gene is a member of the septin gene family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins ...
,
SEPT5
Septin-5 is a protein that in humans is encoded by the ''SEPT5'' gene.
Function
This gene is a member of the septin gene family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins a ...
), (ii)
SEPT3
Neuronal-specific septin-3 is a protein that in humans is encoded by the ''SEPT3'' gene.
Function
This gene belongs to the septin family of GTPases. Members of this family are required for cytokinesis. Expression is upregulated by retinoic aci ...
(
SEPT9
Septin-9 is a protein that in humans is encoded by the ''SEPT9'' gene.
Interactions
SEPT9 has been shown to interact with SEPT2 and SEPT7.
Function
Along with AHNAK, eIF4E and S100A11, SEPT9 has been shown to be essential for pseudopod pr ...
,
SEPT12
Septin 12 is a protein that in humans is encoded by the SEPT12 gene.
Function
This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytos ...
), (iii)
SEPT6
Septin-6 is a protein that in humans is encoded by the ''SEPT6'' gene.
Function
This gene is a member of the septin family of GTPases. Members of this family are required for cytokinesis. This gene encodes four transcript variants encoding thr ...
(
SEPT8
Septin-8 is a protein that in humans is encoded by the ''SEPT8'' gene.
Function
SEPT8 is a member of the highly conserved septin family. Septins are 40- to 60-kD GTPases that assemble as filamentous scaffolds. They are involved in the organiza ...
,
SEPT10
Septin 10 is a protein that in humans is encoded by the SEPT10 gene.
Function
This gene encodes a member of the septin family of cytoskeletal proteins with GTPase activity. This protein localizes to the cytoplasm
In cell biology, the cyto ...
,
SEPT11
Septin-11 is a protein that in humans is encoded by the ''SEPT11'' 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 ...
,
SEPT14
Septin 14 is a protein that in humans is encoded by the ''SEPT14'' gene.
Function
SEPT14 is a member of the highly conserved septin family of GTP-binding cytoskeletal proteins implicated in membrane transport, apoptosis, cell polarity, cell c ...
), and (iv)
SEPT7
Septin-7 is a protein that in humans is encoded by the ''SEPT7'' gene.
Function
This gene encodes a protein that is highly similar to the CDC10 protein of ''Saccharomyces cerevisiae''. The protein also shares similarity with Diff 6 of ''Drosoph ...
. Septin protein complexes are assembled to form either hetero-
hexamer
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...
s (incorporating monomers selected from three different groups and the monomer from each group is present in two copies; 3 x 2 = 6) or hetero-
octamer
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...
s (monomers from four different groups, each monomer present in two copies; 4 x 2 = 8). These hetero-oligomers in turn form higher-order structures such as filaments and rings.
Septins form cage-like structures around
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l
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 ...
s, immobilizing harmful
microbe
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s and preventing them from invading healthy cells. This cellular defence system could potentially be exploited to create therapies for
dysentery
Dysentery (UK pronunciation: , US: ), historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications ...
and other
illness
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that ar ...
es. For example, ''
Shigella
''Shigella'' is a genus of bacteria that is Gram-negative, facultative anaerobic, non-spore-forming, nonmotile, rod-shaped, and genetically closely related to ''E. coli''. The genus is named after Kiyoshi Shiga, who first discovered it in 1897. ...
'' is a
bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
that causes lethal
diarrhoea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
in humans. To propagate from cell to cell, ''Shigella'' bacteria develop
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, 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 ...
-
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 ...
'tails', which propel the microbes and allow them to gain entry into neighbouring host cells. As part of the immune response, human cells produce a cell-signalling protein called
TNF-α
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
which trigger thick bundles of septin filaments to encircle the microbes within the infected host cell.
Microbes that become trapped in these septin cages are broken down by
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
.
Disruptions in septins and
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s in 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 ba ...
s that code for them could be involved in causing
leukaemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
,
colon cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
and neurodegenerative conditions such as
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
and
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. Potential therapies for these, as well as for bacterial conditions such as dysentery caused by ''Shigella'', might bolster the body’s
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 splinte ...
with
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
s that mimic the behaviour of TNF-α and allow the septin cages to proliferate.
''Caenorhabditis elegans''
In the nematode worm ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
'' there are two
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 ba ...
s coding for septins, and septin complexes contain the two different septins in a tetrameric UNC59-UNC61-UNC61-UNC59 complex. Septins in ''C.elegans'' concentrate at the
cleavage furrow
In cell biology, the cleavage furrow is the indentation of the cell's surface that begins the progression of cleavage, by which animal and some algal cells undergo cytokinesis, the final splitting of the membrane, in the process of cell division. ...
and the
spindle midbody during
cell division
Cell division is the process by which a parent cell (biology), 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 eukar ...
. Septins are also involved in cell migration and axon guidance in ''C.elegans''.
In mitochondria
The septin localized in the
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
is called mitochondrial septin (M-septin). It was identified as a
CRMP/CRAM-interacting protein in the developing rat brain.
History
The septins were discovered in 1970 by
Leland H. Hartwell
Leland Harrison (Lee) Hartwell (born October 30, 1939 in Los Angeles, California) is former president and director of the Fred Hutchinson Cancer Research Center in Seattle, Washington. He shared the 2001 Nobel Prize in Physiology or Medicine wit ...
and colleagues in a screen for temperature-sensitive
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s affecting
cell division
Cell division is the process by which a parent cell (biology), 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 eukar ...
(cdc mutants) in yeast (''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
''). The screen revealed four mutants which prevented
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
at restrictive temperature. The corresponding
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 ba ...
s represent the four original septins, ''ScCDC3, ScCDC10, ScCDC11,'' and ''ScCDC12''.
Despite disrupted cytokinesis, the
cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
continued
budding
Budding or blastogenesis is a type of asexual reproduction in which a new organism develops from an outgrowth or bud due to cell division at one particular site. For example, the small bulb-like projection coming out from the yeast cell is know ...
,
DNA synthesis
DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occur ...
, and
nuclear division
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
, which resulted in large
multinucleate
Multinucleate cells (also known as multinucleated or polynuclear cells) are eukaryotic cells that have more than one nucleus per cell, i.e., multiple nuclei share one common cytoplasm. Mitosis in multinucleate cells can occur either in a coordinat ...
cells with multiple, elongated buds. In 1976, analysis of electron
micrograph
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a mic ...
s revealed ~20 evenly spaced
striation
Striations means a series of ridges, furrows or linear marks, and is used in several ways:
* Glacial striation
* Striation (fatigue), in material
* Striation (geology), a ''striation'' as a result of a geological fault
* Striation Valley, in Anta ...
s of 10-nm
filament
The word filament, which is descended from Latin ''filum'' meaning " thread", is used in English for a variety of thread-like structures, including:
Astronomy
* Galaxy filament, the largest known cosmic structures in the universe
* Solar filament ...
s around the mother-bud neck in wild-type but not in septin-mutant cells.
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...
studies revealed that the septin
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, respo ...
s
colocalize into a septin ring at the neck.
The localization of all four septins is disrupted in conditional ''Sccdc3'' and ''Sccdc12'' mutants, indicating interdependence of the septin proteins. Strong support for this finding was provided by
biochemical
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...
studies: The four original septins
co-purified on
affinity columns, together with a fifth septin protein, encoded by ''ScSEP7'' or ''ScSHS1''.
Purified septins from budding yeast,
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
,
Xenopus
''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...
, and
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
ian cells are able to self associate ''
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 an ...
'' to form filaments.
How the septins interact ''in vitro'' to form
hetero-oligomers that assemble into filaments was studied in detail in ''S. cerevisiae''.
Micrographs of purified filaments raised the possibility that the septins are organized in parallel to the mother-bud axis. The 10-nm striations seen on electron micrographs may be the result of lateral interaction between the filaments. Mutant strains lacking factors important for septin organization support this view. Instead of continuous rings, the septins form bars oriented along the mother-bud axis in deletion mutants of ''ScGIN4, ScNAP1'' and ''ScCLA4''.
References
Further reading
*
*
*
*
*
*
*
{{refend
Cell biology
Cell cycle
Proteins
Cellular processes
Cytoskeleton