Vesicle fusion is the merging of a vesicles with a cell membrane. It is the end stage of secretion from secretory vesicles, where their contents are expelled from the cell through exocytosis at the porosome. Vesicles can also fuse with other target cell compartments, such as a lysosome.
Vesicle fusion mainly depends on SNARE proteins in the presence of increased intracellular calcium (Ca2+) concentration.
Triggers
Stimuli that trigger vesicle fusion act by increasing intracellular Ca2+.
- Synaptic vesicles commit vesicle fusion by a nerve impulse reaching the synapse, activating voltage-dependent calcium channels that cause influx of Ca2+ into the cell.
- In the endocrine system, many hormones are released by their releasing hormones binding to G protein coupled receptors coupled to the Gq alpha subunit, activating the IP3/DAG pathway to increase Ca2+. Examples of this mechanism include:
- Gonadotropin releasing hormone [1]
- Thyrotropin releasing hormone[1]
- Growth hormone releasing hormone[1] (minor pathway - main one is cAMP dependent pathway [2])
Mechanism
Assembly of the SNAREs into the "trans" complexes likely bridges the opposing lipid bilayers of membranes belonging to cell and secretory granule, bringing them in proximity and inducing their fusion. The influx of calcium into the cell triggers the completion of the assembly reaction, which is mediated by an interaction between the putative calcium sensor, synaptotagmin, with membrane lipids and/or the partially assembled SNARE complex.
According to the "zipper" hypothesis, the complex assembly starts at the N-terminal parts of SNARE motifs and proceeds towards the C-termini that anchor interacting proteins in membranes. Formation of the "trans"-SNARE complex proceeds through an intermediate complex composed of SNAP-25 and syntaxin-1, which later accommodates synaptobrevin-2 (the quoted syntaxin and synaptobrevin isotypes participate in neuronal neuromediator release).
Based on the stability of the resultant cis-SNARE complex, it has been postulated that energy released during the assembly process serves as a means for overcoming the repulsive forces between the membranes. There are several models that propose explanation of a subsequent step – the formation of stalk and fusion pore, but the exact nature of these processes remains debated. It has, however, been proven that in vitro syntaxin per se is sufficient to drive spontaneous calcium independent fusion of synaptic vesicles containing v-SNAREs.[3] This suggests that in Ca2+-dependent neuronal exocytosis synaptotagmin is a dual regulator, in absence of Ca2+ ions to inhibit SNARE dynamics, while in presence of Ca2+ ions to act as agonist in the membrane fusion process.
References
- ^ a b c Page 237 in: Costanzo, Linda S. (2007). Physiology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7311-3.
- ^ Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-2328-3.
- ^ Woodbury DJ, Rognlien K (2000). "The t-SNARE syntaxin is sufficient for spontaneous fusion of synaptic vesivles to planar membranes". Cell Biology International 24 (11): 809–818. doi:.
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