The Synaptic Vesicle Release Machinery

Annu Rev Biophys. 2015;44:339-67. doi: 10.1146/annurev-biophys-060414-034057.

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 NSF-SNAPs. 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 NSF-SNAP-resistant 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 Ca(2+), 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.

Keywords: Complexin; Munc13; Munc18; SNAREs; Synaptotagmin; membrane fusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Membrane Fusion
  • Nerve Tissue Proteins / metabolism
  • Protein Binding
  • SNARE Proteins / metabolism*
  • Synaptic Transmission
  • Synaptic Vesicles / chemistry
  • Synaptic Vesicles / metabolism*
  • Synaptotagmins / metabolism

Substances

  • Nerve Tissue Proteins
  • SNARE Proteins
  • Synaptotagmins