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

Uri Ashery, Frederique Varoqueaux, Thomas Voets, Andrea Betz, Pratima Thakur, Henriette Koch, Erwin Neher, Nils Brose, Jens Rettig

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3586-3596
Number of pages11
JournalEMBO Journal
Volume19
Issue number14
DOIs
StatePublished - 17 Jul 2000
Externally publishedYes

Keywords

  • Capacitance measurements
  • Exocytosis
  • Munc13-1
  • Priming
  • Secretion

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