Exocytosis (//; from Greek ἔξω "out" and English cyto- "cell" from Gk. κύτος "receptacle") is the durable, energy-consuming process by which a cell directs the contents of secretory vesicles out of the cell membrane and into the extracellular space. These membrane-bound vesicles contain soluble proteins to be secreted to the extracellular environment, as well as membrane proteins and lipids that are sent to become components of the cell membrane. However, the mechanism of the secretion of intravesicular contents out of the cell is very different from the incorporation in the cell membrane of ion channels, signaling molecules, or receptors. While for membrane recycling and the incorporation in the cell membrane of ion channels, signaling molecules, or receptors complete membrane merger is required, for cell secretion there is transient vesicle fusion with the porosome at the cell membrane in a process called exocytosis, dumping its contents out of the cell's environment. 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, 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.1
In multicellular organisms there are two types of exocytosis: 1) Ca2+ triggered non-constitutive (i.e., regulated exocytosis) and 2) non-Ca2+ triggered constitutive. Exocytosis in neuronal chemical synapses is Ca2+ triggered and serves interneuronal signalling. Constitutive exocytosis is performed by all cells and serves the release of components of the extracellular matrix, or just delivery of newly synthesized membrane proteins that are incorporated in the plasma membrane after the fusion of the transport vesicle. Regulated exocytosis, on the other hand, requires an external signal, a specific sorting signal on the vesicles, a clathrin coat, as well as an increase in intracellular calcium. Exocytosis is the opposite of endocytosis. 3) Vesicular exocytosis in prokaryotic gram negative microbes is the latest finding in exocytosis. Herein, periplasm of gram negative microbes is pinched off as outer membrane bound vesicles (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 occuring at the host-pathogen interface, also breaks the myth that exocytosis is purely a eukaryotic cell phenomenon.2
Five steps are involved in exocytosis:
Certain vesicle-trafficking steps require the transportation of a vesicle over a moderately small distance. For example, vesicles that have the duty to transport the proteins from the Golgi apparatus to the cell surface area, will be likely to use motor proteins and a cytoskeletal track to get closer than previously stated 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, due to the fact that 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.
It is useful to distinguish between the initial, loose tethering of vesicles with 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.
The vesicles are also involved in regular cell's transcription processes.
Secretory vesicles transiently dock at the cell plasma membrane, preceding the formation of a tight t-/v-SNARE complex, leading to priming and the establishment of continuity between the opposing bilayers.
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.
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.
- Proteins 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.
Retrieval of synaptic vesicles occurs by endocytosis. Some synaptic vesicles are recycled without a full fusion into the membrane (kiss-and-run fusion), while others require a complete reformation of synaptic vesicles from the membrane by a specialized complex of proteins (clathrin). Non-constitutive exocytosis and subsequent endocytosis are highly energy expending processes, and thus, are dependent on mitochondria.3
- Boron, WF & Boulpaep, EL (2012), Medical Physiology. A Cellular and Molecular Approach 2, Philadelphia: Elsevier
- YashRoy R.C.(1998). Discovery of vesicular exocytosis in prokaryotes and its role in Salmonella invasion. Current Science, vol 75(10), pp 1062-1066.http://www.currentscience.ac.in/cs/Downloads/article_id_075_10_1062_1066_0.pdf
- Ivannikov, M. et al. (2013). "Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume". J. Mol. Neurosci. 49 (1): 223–230. doi:10.1007/s12031-012-9848-8. PMID 22772899.
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- Secretory pathway
- Kiss-and-run fusion
- Endocytic cycle
- Membrane nanotube
- Active Transport
- Viral shedding
- Presynaptic active zone
- Residual body
- Membrane vesicle trafficking
- Host-pathogen interface