Summary: Synaptic vesicle fusion
Josep Rizo1 & Christian Rosenmund2
The core of the neurotransmitter release machinery is formed by SNARE complexes, which bring the vesicle and plasma membranes
together and are key for fusion, and by Munc18-1, which controls SNARE-complex formation and may also have a direct role in
fusion. In addition, SNARE complex assembly is likely orchestrated by Munc13s and RIMs, active-zone proteins that function in
vesicle priming and diverse forms of presynaptic plasticity. Synaptotagmin-1 mediates triggering of release by Ca2+, probably through
interactions with SNAREs and both membranes, as well as through a tight interplay with complexins. Elucidation of the release
mechanism will require a full understanding of the network of interactions among all these proteins and the membranes.
The immense variety and complexity of the functions performed by
the nervous system rely on the ability of neurons to communicate with
each other in defined and precisely timed patterns. Such precise
timing is enabled in part by the fast speed of synaptic transmission.
It takes as little as 100 ms from the arrival of an action potential to the
release of neurotransmitters by Ca2+-evoked synaptic vesicle exo-
cytosis1. These high speeds arise because, after synaptic vesicles dock
onto specialized sites of the plasma membrane called active zones, a
priming reaction(s) leaves the vesicles in a metastable state that is
ready for fast Ca2+-triggered fusion with the plasma membrane.
Neurotransmitter release does not just constitute a means to send
signals between neurons; acute, dynamic as well as long-term changes