Abstract
Extensive research has yielded crucial insights into the mechanism of neurotransmitter release, and working models for the functions of key proteins involved in release. The SNAREs Syntaxin-1, Synaptobrevin, and SNAP-25 play a central role in membrane fusion, forming SNARE complexes that bridge the vesicle and plasma membranes and that are disassembled by NSFSNAPs. Exocytosis likely starts with Syntaxin-1 folded into a self-inhibited closed conformation that binds to Munc18-1. Munc13s open Syntaxin-1, orchestrating SNARE complex assembly in an NSFSNAPresistant manner together with Munc18-1. In the resulting primed state, with partially assembled SNARE complexes, fusion is inhibited by Synaptotagmin-1 and Complexins, which also perform active functions in release. Upon influx of Ca2, Synaptotagmin-1 activates fast release, likely by relieving the inhibition caused by Complexins and cooperating with the SNAREs in bringing the membranes together. Although alternative models exist and fundamental questions remain unanswered, a definitive description of the basic release mechanism may be available soon.
Original language | English (US) |
---|---|
Pages (from-to) | 339-367 |
Number of pages | 29 |
Journal | Annual Review of Biophysics |
Volume | 44 |
DOIs | |
State | Published - Jun 22 2015 |
Keywords
- Complexin
- Membrane fusion
- Munc13
- Munc18
- SNAREs
- Synaptotagmin
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Bioengineering
- Biochemistry
- Cell Biology