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Exocytosis () is a form of active transport and bulk transport in which a cell transports
molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and b ...
s (e.g., neurotransmitters and
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) out of the cell ('' exo-'' + ''
cytosis -Cytosis is a suffix thet either refers to certain aspects of cells ie cellular process or phenomenon or sometimes refers to predominance of certain type of cells. Sometimes it may be shortened to -osis (necrosis, apoptosis) and may be related t ...
''). As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most
chemical substance A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wit ...
s important to them are large
polar Polar may refer to: Geography Polar may refer to: * Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates *Polar climate, the cli ...
molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell. In exocytosis, membrane-bound secretory
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 ...
are carried to the cell membrane, where they dock and fuse at porosomes and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. This secretion is possible because the vesicle transiently fuses with the plasma membrane. In the context of neurotransmission, neurotransmitters are typically released from synaptic vesicles into the synaptic cleft via exocytosis; however, neurotransmitters can also be released via reverse transport through membrane transport proteins. Exocytosis is also a mechanism by which cells are able to insert membrane proteins (such as ion channels and cell surface receptors), lipids, and other components into the cell membrane. Vesicles containing these membrane components fully fuse with and become part of the outer cell membrane.


History

The term was proposed by De Duve in 1963.


Types

In eukaryotes there are two types of exocytosis: 1) Ca2+ triggered non-constitutive (i.e., regulated exocytosis) and 2) non-Ca2+ triggered constitutive (i.e., non-regulated). '' Ca2+ triggered non-constitutive'' exocytosis requires an external signal, a specific sorting signal on the vesicles, a clathrin coat, as well as an increase in intracellular calcium. In multicellular organisms, this mechanism initiates many forms of intercellular communication such as synaptic transmission, hormone secretion by neuroendocrine cells, and immune cells secretion. In neurons and endocrine cells, the SNARE-proteins and SM-proteins catalyze the fusion by forming a complex that brings the two fusion membranes together. For instance, in synapses, the SNARE complex is formed by syntaxin-1 and
SNAP25 Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (''N''-ethylmaleimide-sensitive factor) Attachment Protein Receptor (t-SNARE) protein encoded by the ''SNAP25'' gene found on chromosome 20p12.2 in humans. SNAP-25 is a com ...
at the plasma membrane and VAMP2 at the vesicle membrane. Exocytosis in neuronal chemical synapses is Ca2+ triggered and serves interneuronal signalling. The calcium sensors that triggers exocytosis might interact either with the SNARE complex or with the phospholipids of the fusing membranes. Synaptotagmin has been recognized as the major sensor for Ca2+ triggered exocytosis in animals. However, synaptotagmin proteins are absent in plants and unicellular eukaryotes. Other potential calcium sensors for exocytosis are EF-hand proteins (Ex: Calmodulin) and C2-domain (Ex: Ferlins, E-synaptotagmin, Doc2b) containing proteins. It is unclear how the differenta calcium sensors can cooperate together and mediate the calcium triggered exocytosis kinetic in a specific fashion. ''Constitutive exocytosis'' is performed by all cells and serves the release of components of the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...
or delivery of newly synthesized membrane proteins that are incorporated in the plasma membrane after the fusion of the transport vesicle. There is no clear consensus about the machinery and molecular processes that drive the formation, budding, translocation and fusion of the post-Golgi vesicles to the plasma membrane. The fusion involves membrane tethering (recognition) and membrane fusion. It is still unclear if the machinery between the constitutive and regulated secretion is different. The machinery required for constitutive exocytosis hasn’t been studying as much as the mechanism of regulated exocytosis. Two tethering complexes are associated with constitutive exocytosis in mammals, ELKS and Exocyst. ELKS is a large coiled-coil protein, also involved in synaptic exocytosis, marking the ‘hotspots’ fusion points of the secretory carriers fusion. Exocyst is an octameric protein complex. In mammals, exocyst components localize in both plasma membrane, and Golgi apparatus and the exocyst proteins are colocalized at the fusion point of the post-Golgi vesicles. The membrane fusion of the constitutive exocytosis, probably, is mediated by SNAP29 and Syntaxin19 at the plasma membrane and YKT6 or VAMP3 at the vesicle membrane. ''Vesicular exocytosis'' in prokaryote
gram negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
is a third mechanism and latest finding in exocytosis. The periplasm is pinched off as
bacterial outer membrane vesicles Bacterial outer membrane vesicles (OMVs) are vesicles of lipids released from the outer membranes of Gram-negative bacteria. These vesicles were the first bacterial membrane vesicles (MVs) to be discovered, while Gram-positive bacteria release ...
(OMVs) for translocating microbial biochemical signals into eukaryotic host cells or other microbes located nearby, accomplishing control of the secreting microbe on its environment - including invasion of host, endotoxemia, competing with other microbes for nutrition, etc. This finding of
membrane vesicle trafficking Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory ...
occurring at the host-pathogen interface also dispels the myth that exocytosis is purely a eukaryotic cell phenomenon.


Steps

Five steps are involved in exocytosis:


Vesicle trafficking

Certain vesicle-trafficking steps require the transportation of a vesicle over a moderately small distance. For example, vesicles that transport proteins from the Golgi apparatus to the cell surface area, will be likely to use motor proteins and a cytoskeletal track to get closer to their target. Before tethering would have been appropriate, many of the proteins used for the active transport would have been instead set for passive transport, because the Golgi apparatus does not require ATP to transport proteins. Both the actin- and the microtubule-base are implicated in these processes, along with several motor proteins. Once the vesicles reach their targets, they come into contact with tethering factors that can restrain them.


Vesicle tethering

It is useful to distinguish between the initial, loose ''tethering'' of vesicles to their objective from the more stable, ''packing'' interactions. Tethering involves links over distances of more than about half the diameter of a vesicle from a given membrane surface (>25 nm). Tethering interactions are likely to be involved in concentrating synaptic vesicles at the synapse.


Vesicle docking

Secretory vesicles transiently dock and fuse at the
porosome 440px 280px Porosomes are cup-shaped supramolecular structures in the cell membranes of eukaryotic cells where secretory vesicles transiently dock in the process of vesicle fusion and secretion. The transient fusion of secretory vesicle membrane ...
at the cell plasma membrane, via a tight t-/v-SNARE ring complex.


Vesicle priming

In neuronal exocytosis, the term ''priming'' has been used to include all of the molecular rearrangements and ATP-dependent protein and lipid modifications that take place after initial docking of a synaptic vesicle but before exocytosis, such that the influx of calcium ions is all that is needed to trigger nearly instantaneous neurotransmitter release. In other cell types, whose secretion is constitutive (i.e. continuous, calcium ion independent, non-triggered) there is no priming.


Vesicle fusion

Transient vesicle fusion is driven by SNARE proteins, resulting in release of vesicle contents into the extracellular space (or in case of neurons in the synaptic cleft). The merging of the donor and the acceptor membranes accomplishes three tasks: *The surface of the plasma membrane increases (by the surface of the fused vesicle). This is important for the regulation of cell size, e.g., during cell growth. *The substances within the vesicle are released into the exterior. These might be waste products or toxins, or signaling molecules like hormones or neurotransmitters during
synaptic transmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...
. *
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 embedded in the vesicle membrane are now part of the plasma membrane. The side of the protein that was facing the ''inside'' of the vesicle now faces the ''outside'' of the cell. This mechanism is important for the regulation of transmembrane and transporters.


Vesicle retrieval

Retrieval of synaptic vesicles occurs by endocytosis. Most synaptic vesicles are recycled without a full fusion into the membrane (
kiss-and-run fusion Kiss-and-run fusion is a type of synaptic vesicle release where the vesicle opens and closes transiently. In this form of exocytosis, the vesicle docks and transiently fuses at the presynaptic membrane and releases its neurotransmitters across the s ...
) via
porosome 440px 280px Porosomes are cup-shaped supramolecular structures in the cell membranes of eukaryotic cells where secretory vesicles transiently dock in the process of vesicle fusion and secretion. The transient fusion of secretory vesicle membrane ...
. Non-constitutive exocytosis and subsequent endocytosis are highly energy expending processes, and thus, are dependent on mitochondria. Examination of cells following secretion using electron microscopy demonstrate increased presence of partially empty vesicles following secretion. This suggested that during the secretory process, only a portion of the vesicular content is able to exit the cell. This could only be possible if the vesicle were to temporarily establish continuity with the cell plasma membrane at porosomes, expel a portion of its contents, then detach, reseal, and withdraw into the cytosol (endocytose). In this way, the secretory vesicle could be reused for subsequent rounds of exo-endocytosis, until completely empty of its contents.


See also

* Endocytosis * Pinocytosis * Phagocytosis *
Membrane nanotube A tunneling nanotube (TNT) or membrane nanotube is a term that has been applied to protrusions that extend from the plasma membrane which enable different animal cells to touch over long distances, sometimes over 100 μm between T cells. Two typ ...
* Viral shedding * Presynaptic active zone * Residual body * Degranulation


References


External links

* {{Membrane transport Cellular processes Neurophysiology Membrane biology