Differential dissociation of G protein heterotrimers

Gregory J. Digby, Pooja R. Sethi, Nevin A. Lambert

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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 Gβγ dimers derived specifically from Gi/o heterotrimers. Since all active heterotrimers are thought to dissociate and release free Gβγ dimers, it is unclear why these channels respond primarily to dimers released by Gi/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 GoA heterotrimers are more effective activators of GIRK channels than Gs heterotrimers when comparable amounts of each are available. We also find that active GoA heterotrimers dissociate more readily than active Gs heterotrimers. Differential dissociation may thus provide a simple explanation for Gα-specific activation of GIRK channels and other Gβγ-sensitive effectors.

Original languageEnglish (US)
Pages (from-to)3325-3335
Number of pages11
JournalJournal of Physiology
Issue number14
StatePublished - Jul 2008

ASJC Scopus subject areas

  • Physiology


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