Munc18-1 promotes large dense-core vesicle docking

Neuron. 2001 Aug 30;31(4):581-91. doi: 10.1016/s0896-6273(01)00391-9.


Secretory vesicles dock at the plasma membrane before Ca(2+) triggers their exocytosis. Exocytosis requires the assembly of SNARE complexes formed by the vesicle protein Synaptobrevin and the membrane proteins Syntaxin-1 and SNAP-25. We analyzed the role of Munc18-1, a cytosolic binding partner of Syntaxin-1, in large dense-core vesicle (LDCV) secretion. Calcium-dependent LDCV exocytosis was reduced 10-fold in mouse chromaffin cells lacking Munc18-1, but the kinetic properties of the remaining release, including single fusion events, were not different from controls. Concomitantly, mutant cells displayed a 10-fold reduction in morphologically docked LDCVs. Moreover, acute overexpression of Munc18-1 in bovine chromaffin cells increased the amount of releasable vesicles and accelerated vesicle supply. We conclude that Munc18-1 functions upstream of SNARE complex formation and promotes LDCV docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • Cattle
  • Cell Membrane / metabolism
  • Chromaffin Cells / metabolism*
  • Chromaffin Cells / ultrastructure
  • Exocytosis / physiology
  • Female
  • Fetus / cytology
  • Gene Deletion
  • Gene Expression / physiology
  • Membrane Potentials / physiology
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Electron
  • Munc18 Proteins
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Patch-Clamp Techniques
  • Pregnancy
  • Synaptic Vesicles / metabolism*
  • Syntaxin 1
  • Vesicular Transport Proteins*


  • Antigens, Surface
  • Munc18 Proteins
  • Nerve Tissue Proteins
  • Stx1a protein, mouse
  • Stxbp1 protein, mouse
  • Syntaxin 1
  • Vesicular Transport Proteins