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Sci. Signal., 21 February 2012
Vol. 5, Issue 212, p. ra15
[DOI: 10.1126/scisignal.2002202]

RESEARCH ARTICLES

RGS Proteins Maintain Robustness of GPCR-GIRK Coupling by Selective Stimulation of the G Protein Subunit Gαo

Huai-hu Chuang1* and Alexander Y. Chuang2

1 Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
2 Lowell High School, 1101 Eucalyptus Drive, San Francisco, CA 94132, USA.

Abstract: Termination of heterotrimeric guanine nucleotide–binding protein (G protein) signaling downstream of activated G protein–coupled receptors (GPCRs) is accelerated by regulator of G protein signaling (RGS) proteins, which act as guanosine triphosphatase (GTPase)–activating proteins (GAPs). Using a Xenopus oocyte expression system, we found that although RGS proteins had a negative effect of accelerating the kinetics of GPCR-coupled potassium ion (K+) channel (GIRK) deactivation, they also had positive effects of increasing the amplitudes and activation kinetics of neurotransmitter-evoked GIRK currents. The RGS box domain alone was sufficient to stimulate neurotransmitter-dependent activation of GIRK currents. Moreover, RGS4 mutants with compromised GAP activity augmented GPCR-GIRK coupling (as assessed by measurement of the GIRK current elicited by neurotransmitter). By accelerating G protein activation kinetics, RGS4 specifically stimulated Gαo, which stimulated GPCR-GIRK coupling despite its GAP activity. Opposing actions of RGS proteins thus both stimulate and inhibit G proteins to modulate the amplitude and kinetics of neurotransmitter-induced GIRK currents, thereby distinguishing the responses to activation of different G protein isoforms.

* To whom correspondence should be addressed. E-mail: huai-hu.chuang{at}cornell.edu

Citation: H.-h. Chuang, A. Y. Chuang, RGS Proteins Maintain Robustness of GPCR-GIRK Coupling by Selective Stimulation of the G Protein Subunit Gαo. Sci. Signal. 5, ra15 (2012).

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