Selective activation of cognate SNAREpins by Sec1/Munc18 proteins

Cell. 2007 Jan 12;128(1):183-95. doi: 10.1016/j.cell.2006.12.016.

Abstract

Sec1/Munc18 (SM) proteins are required for every step of intracellular membrane fusion, but their molecular mechanism of action has been unclear. In this work, we demonstrate a fundamental role of the SM protein: to act as a stimulatory subunit of its cognate SNARE fusion machinery. In a reconstituted system, mammalian SNARE pairs assemble between bilayers to drive a basal fusion reaction. Munc18-1/nSec1, a synaptic SM protein required for neurotransmitter release, strongly accelerates this reaction through direct contact with both t- and v-SNAREs. Munc18-1 accelerates fusion only for the cognate SNAREs for exocytosis, therefore enhancing fusion specificity.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Exocytosis
  • Humans
  • Membrane Fusion
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism
  • Munc18 Proteins / metabolism*
  • Mutation / genetics
  • Neurons / cytology
  • Protein Binding
  • Protein Subunits / metabolism
  • Rats
  • SNARE Proteins / metabolism*
  • Syntaxin 1 / chemistry
  • Syntaxin 1 / metabolism
  • Vesicle-Associated Membrane Protein 2 / chemistry
  • Vesicle-Associated Membrane Protein 2 / genetics
  • Vesicle-Associated Membrane Protein 2 / metabolism

Substances

  • Multiprotein Complexes
  • Munc18 Proteins
  • Protein Subunits
  • SNARE Proteins
  • Syntaxin 1
  • Vesicle-Associated Membrane Protein 2