Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission

EMBO J. 2012 May 2;31(9):2156-68. doi: 10.1038/emboj.2012.72. Epub 2012 Mar 23.


Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Mice, Knockout
  • Munc18 Proteins / physiology*
  • Neurons / physiology
  • Point Mutation
  • Protein Binding
  • SNARE Proteins / physiology*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles


  • Munc18 Proteins
  • SNARE Proteins