Munc13-1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells

EMBO J. 2000 Jul 17;19(14):3586-96. doi: 10.1093/emboj/19.14.3586.

Abstract

In chromaffin cells the number of large dense-core vesicles (LDCVs) which can be released by brief, intense stimuli represents only a small fraction of the 'morphologically docked' vesicles at the plasma membrane. Recently, it was shown that Munc13-1 is essential for a post-docking step of synaptic vesicle fusion. To investigate the role of Munc13-1 in LDCV exocytosis, we overexpressed Munc13-1 in chromaffin cells and stimulated secretion by flash photolysis of caged calcium. Both components of the exocytotic burst, which represent the fusion of release-competent vesicles, were increased by a factor of three. The sustained component, which represents vesicle maturation and subsequent fusion, was increased by the same factor. The response to a second flash, however, was greatly reduced, indicating a depletion of release-competent vesicles. Since there was no apparent change in the number of docked vesicles, we conclude that Munc13-1 acts as a priming factor by accelerating the rate constant of vesicle transfer from a pool of docked, but unprimed vesicles to a pool of release-competent, primed vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain
  • Calcium / metabolism
  • Catecholamines / metabolism
  • Cattle
  • Cells, Cultured
  • Chromaffin Cells / cytology*
  • Chromaffin Cells / metabolism
  • Computer Simulation
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / metabolism
  • Electric Conductivity
  • Exocytosis*
  • Kinetics
  • Membrane Fusion
  • Microscopy, Electron
  • Models, Biological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Patch-Clamp Techniques
  • Photolysis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rats
  • Synaptic Vesicles / metabolism
  • Synaptosomes / metabolism
  • Vacuoles / metabolism*

Substances

  • Catecholamines
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Unc13a protein, rat
  • 2-nitrophenyl-EGTA
  • Egtazic Acid
  • Calcium