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

Jose Rizo-Rey, Thomas C. Südhof

Research output: Contribution to journalArticle

254 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)279-308
Number of pages30
JournalAnnual Review of Cell and Developmental Biology
Volume28
DOIs
StatePublished - Dec 3 2012

Keywords

  • active zone
  • molecular chaperones
  • neurotransmitter release
  • presynaptic plasticity
  • synaptic vesicle exocytosis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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