Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis
- Max-Planck-Institut fuer Experimentelle Medizin, Germany
- Leibniz-Institute for Molecular Pharmacology, Germany
- University of Copenhagen, Denmark
- Saarland University, 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 Ca2+-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.
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Animal experimentation: All experiments were performed in compliance with the regulations of the local Animal Care and Use Committee of Lower Saxony, Oldenburg, Germany.
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© 2015, Man et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis
eLife 4:e10635.
https://doi.org/10.7554/eLife.10635
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