Source:http://linkedlifedata.com/resource/pubmed/id/17202488
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-1-4
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pubmed:abstractText |
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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/UNC13B protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1529-2401
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
212-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17202488-Animals,
pubmed-meshheading:17202488-Calcium Channels,
pubmed-meshheading:17202488-Cattle,
pubmed-meshheading:17202488-Cells, Cultured,
pubmed-meshheading:17202488-Chromaffin Cells,
pubmed-meshheading:17202488-Exocytosis,
pubmed-meshheading:17202488-Long-Term Potentiation,
pubmed-meshheading:17202488-Nerve Tissue Proteins,
pubmed-meshheading:17202488-Receptors, G-Protein-Coupled,
pubmed-meshheading:17202488-Type C Phospholipases
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pubmed:year |
2007
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pubmed:articleTitle |
Potentiation of exocytosis by phospholipase C-coupled G-protein-coupled receptors requires the priming protein Munc13-1.
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pubmed:affiliation |
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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