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PMID: 17202488 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Potentiation of exocytosis by phospholipase C-coupled G-protein-coupled receptors requires the priming protein Munc13-1.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 1 ·2007-01-03 ·Pages 212-9

Bauer CS, Woolley RJ, Teschemacher AG, Seward EP

Abstract

The vesicle priming protein Munc13-1 is regulated by diacylglycerol (DAG) and is therefore hypothesized to play a role in the control of neurotransmitter release by phospholipase C (PLC)-coupled receptors. We combined voltage-clamp recordings of voltage-gated Ca2+ channels (VGCCs) and high-resolution capacitance measurements to investigate the mechanism of receptor-mediated modulation of exocytosis in bovine chromaffin cells. Activation of endogenous H1 G(q)-protein-coupled receptors (G(q)PCRs) by histamine potentiated stimulus-coupled secretion despite concurrently inhibiting Ca2+ influx through VGCCs. Histamine increased the size of the readily releasable pool of vesicles and in particular a subpool of fusion-competent vesicles localized in close proximity to VGCCs. Pharmacological characterization showed that potentiation of exocytosis depended on the activation of PLC but not protein kinase C. Overexpression of wild-type Munc13-1 by adenoviral infection had no effect on histamine-induced potentiation per se, whereas DAG-insensitive Munc13-1(H567K) completely abolished it. This is the first endogenous mammalian G(q)PCR signaling pathway identified that engages Munc13-1 to increase stimulus-coupled secretion by recruiting vesicles to the immediately releasable pool. G(q)PCRs are therefore able to control exocytosis at the level of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex formation to produce rapid, short-term potentiation of the secretory output of neurons and endocrine cells.

MeSH Terms
Animals Calcium Channels/physiology Cattle Cells, Cultured Chromaffin Cells/physiology Exocytosis/physiology Long-Term Potentiation/physiology Nerve Tissue Proteins/metabolism Receptors, G-Protein-Coupled/metabolism Type C Phospholipases/metabolism
Chemicals
Calcium Channels Nerve Tissue Proteins Receptors, G-Protein-Coupled UNC13B protein, human Type C Phospholipases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bauer Claudia S
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Woolley Robert J
Teschemacher Anja G
Seward Elizabeth P
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4201-06.2007
Published
2007-01-03
Pages
212-9
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6672273
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4201-06.2007 PMC Full Text View journal details
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