Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly

Nat Commun. 2019 Jan 8;10(1):69. doi: 10.1038/s41467-018-08028-6.


The transition of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive. Here, we identify an interaction between Munc13-1 and the membrane-proximal linker region of synaptobrevin-2, and reveal its essential role in transition and exocytosis. Upon this interaction, Munc13-1 not only recruits synaptobrevin-2-embedded vesicles to the target membrane but also renders the synaptobrevin-2 SNARE motif more accessible to the Munc18-1/syntaxin-1 complex. Afterward, the entry of SNAP-25 leads to a half-zippered SNARE assembly, which eventually dissociates the Munc18-1/syntaxin-1 complex to complete SNARE complex formation. Our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exocytosis
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Mice
  • Munc18 Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons
  • Primary Cell Culture
  • Protein Binding / physiology
  • Protein Domains / physiology
  • Synaptosomal-Associated Protein 25 / metabolism*
  • Syntaxin 1 / metabolism*
  • Vesicle-Associated Membrane Protein 2 / metabolism*


  • Munc18 Proteins
  • Nerve Tissue Proteins
  • SNAP25 protein, human
  • Stx1a protein, rat
  • Stxbp1 protein, rat
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Unc13a protein, mouse
  • Unc13a protein, rat
  • Vamp2 protein, rat
  • Vesicle-Associated Membrane Protein 2