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J Physiol. 2008 Jul 15;586(14):3325-35. doi: 10.1113/jphysiol.2008.153965. Epub 2008 May 22.

Differential dissociation of G protein heterotrimers.

Author information

1
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30809, USA.

Abstract

Signalling by heterotrimeric G proteins is often isoform-specific, meaning certain effectors are regulated exclusively by one family of heterotrimers. For example, in excitable cells inwardly rectifying potassium (GIRK) channels are activated by G betagamma dimers derived specifically from G(i/o) heterotrimers. Since all active heterotrimers are thought to dissociate and release free G betagamma dimers, it is unclear why these channels respond primarily to dimers released by G(i/o) heterotrimers. We reconstituted GIRK channel activation in cells where we could quantify heterotrimer expression at the plasma membrane, GIRK channel activation, and heterotrimer dissociation. We find that G(oA) heterotrimers are more effective activators of GIRK channels than G(s) heterotrimers when comparable amounts of each are available. We also find that active G(oA) heterotrimers dissociate more readily than active G(s) heterotrimers. Differential dissociation may thus provide a simple explanation for G alpha-specific activation of GIRK channels and other G betagamma-sensitive effectors.

PMID:
18499725
PMCID:
PMC2538816
DOI:
10.1113/jphysiol.2008.153965
[Indexed for MEDLINE]
Free PMC Article

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