Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26575293.
- Also identified by DOI 10.7554/eLife.10635 and PMC identifier 4798968.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Chromaffin Cells
- Exocytosis
- Intracellular Signaling Peptides and Proteins
- Nerve Tissue Proteins
- Secretory Vesicles