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

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

Author information

1
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
2
Leibniz Institute for Molecular Pharmacology, Berlin, Germany.
3
Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences and Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
4
Department of Physiology, Saarland University, Homburg, Germany.

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

PMID:
26575293
PMCID:
PMC4798968
DOI:
10.7554/eLife.10635
[Indexed for MEDLINE]
Free PMC Article

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