Synaptic Vesicle Fusion


Neurotransmitter release from synaptic terminals occurs by the rapid, calcium‐dependent fusion of transmitter‐containing synaptic vesicles with the presynaptic membrane. The core machinery that mediates membrane fusion is thought to consist of the neuronal SNARE proteins (VAMP/synaptobrevin, syntaxin and SNAP‐25). Accessory proteins operate at various stages to mediate the priming of vesicles to fusion competence (NSF/SNAP, munc18, munc13) and the detection of calcium increases that trigger fusion (synaptotagmin).

Keywords: synaptic vesicle; membrane fusion; exocytosis; neurotransmitter secretion; calcium regulation

Figure 1.

Molecular mechanisms underlying synaptic vesicle exocytosis. A reserve pool of synaptic vesicles (1), linked to actin by synapsin, is recruited to docking sites at the active zone by vesicle detachment followed by movement via myosin motors. Following vesicle docking at the presynaptic active zone (2), vesicles are rendered fusion‐competent by a series of priming steps (2 → 5 or 6) that may involve ATP‐dependent, NSF‐mediated disassembly of cis SNARE complexes (2 → 3), ATP‐dependent synthesis of PI(4,5)P2 (2 → 3), munc18 dissociation from syntaxin possibly catalysed by munc13 (3 → 4), and the formation of loosely assembled (4 → 5) or fully assembled (4 → 6) trans SNARE complexes. Ca2+ triggering of fusion is depicted as mediated through synaptotagmins on either vesicle or presynaptic membrane. Ca2+ binding to synaptotagmins could promote formation of fully assembled trans SNARE complexes and fusion (5 → 7). Alternatively, a fully assembled trans SNARE complex that initiated hemi‐fusion (6) could be acted upon by Ca2+‐bound synaptotagmin to promote transition to fusion pore formation and full fusion (6 → 7). Subsequent dilation of the fusion pore and release of neurotransmitter is depicted in (8).



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Martin, Thomas FJ(Feb 2003) Synaptic Vesicle Fusion. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000209]