The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged?

Annu Rev Cell Dev Biol. 2012;28:279-308. doi: 10.1146/annurev-cellbio-101011-155818.

Abstract

Neurotransmitter release is governed by proteins that have homo-logs in most types of intracellular membrane fusion, including the Sec1/Munc18 protein Munc18-1 and the SNARE proteins syntaxin-1, synaptobrevin/VAMP, and SNAP-25. The SNAREs initiate fusion by forming tight SNARE complexes that bring the vesicle and plasma membranes together. SNARE maintenance in a functional state depends on two chaperone systems (Hsc70/αCSP/SGT and synuclein); defects in these systems lead to neurodegeneration. Munc18-1 binds to an autoinhibitory closed conformation of syntaxin-1, gating formation of SNARE complexes, and also binds to SNARE complexes, which likely underlies the crucial function of Munc18-1 in membrane fusion by an as-yet unclear mechanism. Syntaxin-1 opening is mediated by Munc13s through their MUN domain, which is homologous to diverse tethering factors and may also have a general role in fusion. MUN domain activity is likely modulated in diverse presynaptic plasticity processes that depend on Ca(2+) and RIM proteins, among others.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cell Membrane / physiology
  • Humans
  • Membrane Fusion*
  • Models, Molecular
  • Molecular Chaperones / metabolism
  • Molecular Chaperones / physiology
  • Munc18 Proteins / metabolism
  • Munc18 Proteins / physiology*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • SNARE Proteins / metabolism
  • SNARE Proteins / physiology*

Substances

  • Molecular Chaperones
  • Munc18 Proteins
  • SNARE Proteins