G protein (beta gamma) directly regulates SNARE protein fusion machinery for secretory granule exocytosis.
The activation of G protein–coupled receptors (GPCRs) can result in an inhibition of Ca21-dependent hormone and neurotransmitter secretion. This has been attributed in part to G protein inhibition of Ca21 influx. However, a frequently dominant inhibitory effect, of unknown mechanism, also occurs distal to Ca21 entry. Here we characterize direct inhibitory actions of G protein bc (Gbc) on Ca21-triggered vesicle exocytosis in permeable PC12 cells. Gbc inhibition was rapid (<1 s) and was attenuated by cleavage of synaptosome-associated protein of 25 kD (SNAP25). Gbc bound soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, and binding was reduced to SNARE complexes containing cleaved SNAP25 or by Ca21-dependent synaptotagmin binding. Here we show inhibitory coupling between GPCRs and vesicle exocytosis mediated directly by Gbc interactions with the Ca21-dependent fusion machinery.
|Main Author:||Blackmer, Trillium.|
|Other Authors:||Larsen, Eric., Bartleson, Cheryl., Kowalchyk, Judith., Yoon, Eun-Ja., Preininger, Anita., Alford,Simon., Hamm, Heidi., Martin, Thomas.|