Potentiation of Exocytosis by Phospholipase C-coupled G-protein-coupled Receptors Requires the Priming Protein Munc13-1.
From: Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Jan 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 1
- Pages: 212-9
- Medium: Internet
- Language: English
- Citation (JAMA): Bauer Claudia S, Woolley Robert J, Teschemacher Anja G, et al. Potentiation of Exocytosis by Phospholipase C-coupled G-protein-coupled Receptors Requires the Priming Protein Munc13-1.. J. Neurosci. Jan 2007;27:212-9
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 Headings (Keywords): Animals, Calcium Channels, Cattle, Cells, Cultured, Chromaffin Cells, Exocytosis, Long-Term Potentiation, Nerve Tissue Proteins, Receptors, G-Protein-Coupled, Type C Phospholipases
Check for Full Text / PubMed Unique Identifier (PMID): 17202488
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