In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 5, No. 212 ( 2012-02-21)
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 Gα o , 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.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.2002202
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2012
