Format

Send to

Choose Destination
Nat Neurosci. 2005 Apr;8(4):421-5. Epub 2005 Mar 20.

G protein betagamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis.

Author information

1
Department of Biological Sciences, University of Illinois at Chicago, 840 West Taylor Street, Chicago, Illinois 60607, USA.

Abstract

The activation of G protein-coupled receptors (GPCRs) can result in an inhibition of Ca(2+)-dependent hormone and neurotransmitter secretion. This has been attributed in part to G protein inhibition of Ca(2+) influx. However, a frequently dominant inhibitory effect, of unknown mechanism, also occurs distal to Ca(2+) entry. Here we characterize direct inhibitory actions of G protein betagamma (Gbetagamma) on Ca(2+)-triggered vesicle exocytosis in permeable PC12 cells. Gbetagamma inhibition was rapid (<1 s) and was attenuated by cleavage of synaptosome-associated protein of 25 kD (SNAP25). Gbetagamma bound soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, and binding was reduced to SNARE complexes containing cleaved SNAP25 or by Ca(2+)-dependent synaptotagmin binding. Here we show inhibitory coupling between GPCRs and vesicle exocytosis mediated directly by Gbetagamma interactions with the Ca(2+)-dependent fusion machinery.

Comment in

PMID:
15778713
DOI:
10.1038/nn1423
[Indexed for MEDLINE]

Publication types, MeSH terms, Substances

Publication types

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center