Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

Elife. 2015 Nov 17;4:e10635. doi: 10.7554/eLife.10635.

Abstract

It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca(2+)-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.

Keywords: baiap3; docking; large dense-core vesicle; mouse; munc13; neuroendocrine; neuroscience; priming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromaffin Cells / metabolism*
  • Exocytosis*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Models, Biological
  • Nerve Tissue Proteins / metabolism*
  • Secretory Vesicles / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Unc13b protein, mouse

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.