Intracellular Transport
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Intracellular transport is the movement of
vesicles 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 ...
and substances within a
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 ...
. Intracellular transport is required for maintaining
homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
within the cell by responding to physiological signals. Proteins synthesized in the cytosol are distributed to their respective organelles, according to their specific amino acid’s sorting sequence.
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 ...
transport packets of components to particular intracellular locations by attaching them to
molecular motor Molecular motors are natural (biological) or artificial molecular machines that are the essential agents of movement in living organisms. In general terms, a motor is a device that consumes energy in one form and converts it into motion or mecha ...
s that haul them along
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 and
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 ...
filaments. Since intracellular transport heavily relies on microtubules for movement, the 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 compos ...
play a vital role in trafficking vesicles between organelles and the plasma membrane by providing mechanical support. Through this pathway, it is possible to facilitate the movement of essential molecules such as membrane‐bounded vesicles and organelles,
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
, and chromosomes. Intracellular transport is unique to eukaryotic cells because they possess organelles enclosed in membranes that need to be mediated for exchange of cargo to take place. Conversely, in
prokaryotic 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 ...
cells, there is no need for this specialized transport mechanism because there are no membranous organelles and compartments to traffic between. Prokaryotes are able to subsist by allowing materials to enter the cell via simple
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 ...
. Intracellular transport is more specialized than diffusion; it is a multifaceted process which utilizes
transport vesicles In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion ( exocytosis), uptake ( endocytosis) and transport of ma ...
. Transport vesicles are small structures within the cell consisting of a fluid enclosed by a
lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
that hold cargo. These vesicles will typically execute cargo loading and vesicle budding, vesicle transport, the binding of the vesicle to a target membrane and the fusion of the vesicle membranes to target membrane. To ensure that these vesicles embark in the right direction and to further organize the cell, special motor proteins attach to cargo-filled vesicles and carry them along the cytoskeleton. For example, they have to ensure that
lysosomal A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...
enzymes are transferred specifically to 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 ins ...
and not to another part of the cell which could lead to deleterious effects.


Fusion

Small membrane bound vesicles responsible for transporting proteins from one organelle to another are commonly found in endocytic and
secretory pathway 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
s. Vesicles bud from their donor organelle and release the contents of their vesicle by a fusion event in a particular target organelle. The endoplasmic reticulum serves as a channel that proteins will pass through bound for their final destination. Outbound proteins from the endoplasmic reticulum will bud off into transport vesicles that travel along 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 ...
to reach their specific destinations. Since the ER is the site of protein synthesis, it would serve as the parent organelle, and the cis face of the golgi, where proteins and signals are received, would be the acceptor. In order for the transport vesicle to accurately undergo a fusion event, it must first recognize the correct target membrane then fuse with that membrane. Rab proteins on the surface of the transport vesicle are responsible for aligning with the complementary tethering proteins found on the respective organelle's cytosolic surface. This fusion event allows for the delivery of the vesicles contents mediated by proteins such as
SNARE SNARE proteins – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle fu ...
proteins. SNAREs are small, tail-anchored proteins which are often post-translationally inserted into membranes that are responsible for the fusion event necessary for vesicles to transport between organelles in the cytosol. There are two forms of SNARES, the t-SNARE and v-SNARE, which fit together similar to a lock and key. The t-SNAREs function by binding to the membranes of the target organelles, while the v-SNAREs function by binding to the vesicle membranes.


Role of endocytosis

Intracellular transport is an overarching category of how cells obtain nutrients and signals. One very well understood form of intracellular transport is known as
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
. Endocytosis is defined as the uptake of material by the invagination of the plasma membrane. More specifically, eukaryotic cells use endocytosis of the uptake of nutrients, down regulation of growth factor receptors’ and as a mass regulator of the signaling circuit. This method of transport is largely intercellular in lieu of uptake of large particles such as bacteria via phagocytosis in which a cell engulfs a solid particle to form an internal vesicle called a phagosome. However, many of these processes have an intracellular component.
Phagocytosis 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 ...
is of great importance to intracellular transport because once a substance is deemed harmful and engulfed in a vesicle, it can be trafficked to the appropriate location for degradation. These endocytosed molecules are sorted into
early endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can f ...
s within the cell, which serves to further sort these substances to the correct final destination (in the same way the Golgi does in the secretory pathway). From here, the early endosome starts a cascade of transport where the cargo is eventually hydrolyzed inside the lysosome for degradation. This capability is necessary for the degradation of any cargo that is harmful or unnecessary for the cell; this is commonly seen in response to foreign material. Phagocytosis has an immunologic function and role in
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
. Additionally, endocytosis can be observed through the nonspecific internalization of fluid droplets via
pinocytosis In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell me ...
and in
receptor mediated endocytosis Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
.


Role of microtubules

The transport mechanism depends on the material being moved. Intracellular transport that requires quick movement will use an actin-myosin mechanism while more specialized functions require microtubules for transport.
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 function as tracks in the intracellular transport of membrane-bound vesicles and organelles. This process is propelled by motor proteins such as
dynein Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements importa ...
. Motor proteins connect the transport vesicles to microtubules and actin filaments to facilitate intracellular movement. Microtubules are organized so their plus ends extend through the periphery of the cells and their minus ends are anchored within the centrosome, so they utilize the motor proteins
kinesin A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...
’s (positive end directed) and
dynein Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements importa ...
’s (negative end directed) to transport vesicles and organelles in opposite directions through the cytoplasm. Each type of membrane vesicle is specifically bound to its own kinesin motor protein via binding within the tail domain. One of the major roles of microtubules is to transport membrane vesicles and organelles through the cytoplasm of eukaryotic cells. It is speculated that areas within the cell considered "microtubule-poor" are probably transported along microfilaments aided by a
myosin 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 ...
motor protein. In this manner, microtubules assist the transport of chromosomes towards the
spindle poles 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 ...
by utilizing the dynein motor proteins during
anaphase Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall maxim ...
.


Diseases

By understanding the components and mechanisms of intracellular transport it is possible to see its implication in diseases. Defects encompass improper sorting of cargo into transport carriers, vesicle budding, issues in movement of vesicles along cytoskeletal tracks, and fusion at the target membrane. Since the life cycle of the cell is a highly regulated and important process, if any component goes awry there is the possibility for deleterious effects. If the cell is unable to correctly execute components of the intracellular pathway there is the impending possibility for protein aggregates to form. Growing evidence supports the concept that deficits in axonal transport contributes to pathogenesis in multiple neurodegenerative diseases. It is proposed that protein aggregations due to faulty transport is a leading cause of the development of
ALS Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...
,
Alzheimer’s Alzheimer's disease (AD) is a 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 remembering recent events. As t ...
and
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. On the other hand, targeting the intracellular transport processes of these motor proteins constitutes the possibility for pharmacological targeting of drugs. By understanding the method in which substances move along neurons or microtubules it is possible to target specific pathways for disease. Currently, many drug companies are aiming to utilize the trajectory of intracellular transport mechanisms to deliver drugs to localized regions and target cells without harming healthy neighboring cells. The potential for this type of treatment in anti-cancer drugs is an exciting, promising area of research.


See also

*
Transport by multiple-motor proteins Transport by molecular motor proteins (Kinesin A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate ( ...
*
Kinesin A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...
* Adaptor protein *
Leelamine Leelamine (dehydroabietylamine) is a diterpene amine that has weak affinity for the cannabinoid receptors CB1 and CB2, as well as being an inhibitor of pyruvate dehydrogenase kinase. Optically active leelamine is also used as a chiral resolvin ...
*
Dynactin Dynactin is a 23 Protein subunit, subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (ACTR1A, Arp1). Discovery Dynactin was identified a ...
*
MCOLN2 Mucolipin-2 also known as TRPML2 (transient receptor potential cation channel, mucolipin subfamily, member 2) is a protein that in humans is encoded by the ''MCOLN2'' gene. It is a member of the small family of the TRPML channels, a subgroup of t ...
*
KIF6 Kinesin family member 6 is a protein that in humans is encoded by the KIF6 gene. This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule Microtubu ...
,
KIF5A Kinesin family member 5A is a protein that in humans is encoded by the ''KIF5A'' gene. This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multi-subunit complex that functions as a microtubule motor ...
, involved in intracellular organelle transport *
COG2 Conserved oligomeric Golgi complex subunit 2 is a protein that in humans is encoded by the ''COG2'' gene. Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modifi ...
,
COG4 Conserved oligomeric Golgi complex subunit 4 is a protein that in humans is encoded by the ''COG4'' gene. Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modif ...
,
COG5 Conserved oligomeric Golgi complex subunit 5 is a protein that in humans is encoded by the ''COG5'' gene. Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modif ...
,
COG7 Conserved oligomeric Golgi complex subunit 7 is a protein that in humans is encoded by the ''COG7'' gene. Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modi ...
*
Sterol carrier protein Sterol carrier proteins (also known as nonspecific lipid transfer proteins) is a family of proteins that transfer steroids and probably also phospholipids and gangliosides between cellular membranes. These proteins are different from plant nonspe ...


References

{{Reflist Cellular processes Cytoskeleton