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

Research output: Contribution to journalJournal articlepeer-review

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.
Original languageEnglish
Article numbere10635
JournaleLife
Volume4
Pages (from-to)1-28
Number of pages28
ISSN2050-084X
DOIs
Publication statusPublished - 17 Nov 2015

ID: 148102260