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

Authors: Man, Kwun Nok M  Imig, Cordelia  Walter, Alexander M  Pinheiro, Paulo S  Stevens, David R  Rettig, Jens  Sørensen, Jakob B  Cooper, Benjamin H  Brose, Nils  Wojcik, Sonja M 
Citation: Man KN, etal., Elife. 2015 Nov 17;4. pii: e10635. doi: 10.7554/eLife.10635.
Pubmed: (View Article at PubMed) PMID:26575293
DOI: Full-text: DOI:10.7554/eLife.10635

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.

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RGD Object Information
RGD ID: 12050107
Created: 2017-01-21
Species: All species
Last Modified: 2017-01-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.