Identification of the minimal protein domain required for priming activity of Munc13-1

Curr Biol. 2005 Dec 20;15(24):2243-8. doi: 10.1016/j.cub.2005.10.055. Epub 2005 Nov 3.


Most nerve cells communicate with each other through synaptic transmission at chemical synapses. The regulated exocytosis of neurotransmitters, hormones, and peptides occurs at specialized membrane areas through Ca2+-triggered fusion of secretory vesicles with the plasma membrane . Prior to fusion, vesicles are docked at the plasma membrane and must then be rendered fusion-competent through a process called priming. The molecular mechanism underlying this priming process is most likely the formation of the SNARE complex consisting of Syntaxin 1, SNAP-25, and Synaptobrevin 2. Members of the Munc13 protein family consisting of Munc13-1, -2, -3, and -4 were found to be absolutely required for this priming process . In the present study, we identified the minimal Munc13-1 domain that is responsible for its priming activity. Using Munc13-1 deletion constructs in an electrophysiological gain-of-function assay of chromaffin-granule secretion, we show that priming activity is mediated by the C-terminal residues 1100-1735 of Munc13-1, which contains both Munc13-homology domains and the C-terminal C2 domain. Priming by Munc13-1 appears to require its interaction with Syntaxin 1 because point mutants that do not bind Syntaxin 1 do not prime chromaffin granules.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blotting, Western
  • Calcium / metabolism
  • Chromaffin Cells
  • Chromaffin Granules / metabolism
  • Electrophysiology
  • Green Fluorescent Proteins
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Protein Structure, Tertiary*
  • Synaptic Transmission / genetics*
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / metabolism*
  • Syntaxin 1 / metabolism


  • Nerve Tissue Proteins
  • Syntaxin 1
  • Unc13a protein, mouse
  • Green Fluorescent Proteins
  • Calcium