Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation

J Neurochem. 2005 Jun;93(6):1393-400. doi: 10.1111/j.1471-4159.2005.03128.x.


Munc18-1, a member of the Sec1/Munc18 (SM) protein family, is essential for synaptic vesicle exocytosis. Munc18-1 binds tightly to the SNARE protein syntaxin 1, but the physiological significance and functional role of this interaction remain unclear. Here we show that syntaxin 1 levels are reduced by 70% in munc18-1 knockout mice. Pulse-chase analysis in transfected HEK293 cells revealed that Munc18-1 directly promotes the stability of syntaxin 1, consistent with a chaperone function. However, the residual syntaxin 1 in munc18-1 knockout mice is still correctly targeted to synapses and efficiently forms SDS-resistant SNARE complexes, demonstrating that Munc18-1 is not required for syntaxin 1 function as such. These data demonstrate that the Munc18-1 interaction with syntaxin 1 is physiologically important, but does not represent a classical chaperone-substrate relationship. Instead, the presence of SNARE complexes in the absence of membrane fusion in munc18-1 knockout mice indicates that Munc18-1 either controls the spatially correct assembly of core complexes for SNARE-dependent fusion, or acts as a direct component of the fusion machinery itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Brain / metabolism
  • Cell Line
  • Exocytosis / physiology*
  • Female
  • Humans
  • Macromolecular Substances / metabolism
  • Male
  • Membrane Fusion / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Chaperones / metabolism
  • Munc18 Proteins
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Presynaptic Terminals / metabolism
  • Protein Transport / physiology
  • SNARE Proteins
  • Synaptic Membranes / metabolism*
  • Synaptic Transmission / physiology
  • Syntaxin 1
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • Antigens, Surface
  • Macromolecular Substances
  • Molecular Chaperones
  • Munc18 Proteins
  • Nerve Tissue Proteins
  • SNARE Proteins
  • STX1A protein, human
  • STXBP1 protein, human
  • Stx1a protein, mouse
  • Stxbp1 protein, mouse
  • Syntaxin 1
  • Vesicular Transport Proteins