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(Circulation Research. 2006;98:585.)
© 2006 American Heart Association, Inc.

Editorials

Specificity and Diversity in G_i/o-Mediated Signaling

How the Heart Operates the RGS Brake Pedal

Thomas Wieland, Stefan Herzig

From the Department of Experimental and Clinical Pharmacology and Toxicology (T.W.), University of Heidelberg, Mannheim, and the Department of Pharmacology (S.H.), University of Cologne, Germany.

Correspondence to Stefan Herzig, Department of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Koeln, Germany. E-mail stefan.herzig@uni-koeln.de

See related article, pages 659–666

Key Words: RGS • G-protein • GPCR • heart rate

An extract of the first 250 words of the full text is provided, because this article has no abstract.

G-Protein–coupled receptors (GPCRs) are involved in the regulation of virtually every physiological process. These receptors operate by catalyzing the GDP/GTP exchange at a coupled heterotrimeric G protein (Gß), thereby promoting the dissociation of the heterotrimer into a free GTP-liganded G-subunit and a Gß dimer. Both G and Gß-dimer then regulate the activity of effectors, eg, second-messenger producing enzymes and ion channels. The duration of G protein activation is primarily controlled by the intrinsic GTPase activity of G. On GTP hydrolysis, G returns to the GDP-bound conformation and reassembles with the Gß dimer. More than 100 different GPCRs have been detected in cardiovascular cells, some of which are coupled to members of the pertussis-toxin (PTX)-sensitive G_i/o subfamily of heterotrimeric G proteins. An intense focus of investigation has been the mechanism(s) by which such a wide array of specific signals can be channeled through a very limited number of multifunctional G protein subunits, and yet retain specificity when reaching their ultimate molecular targets, such as enzymes or ion channels. In recent years, such "preferential coupling" has been attributed to spatially restricted signaling complexes, formed in lipid rafts and caveolae, and held together by anchoring or scaffolding proteins.

Within this context, regulators of G protein signaling (RGS) proteins are of particular interest. RGS proteins were first identified as GTPase Activating Proteins (GAPs) which speed up GTP hydrolysis of G, but they also serve as protein scaffolds.^1,2 RGS proteins contribute to the complexity in G_i/o-mediated signaling. All . . . [Full Text of this Article]

Related Article:

Endogenous RGS Proteins and G Subtypes Differentially Control Muscarinic and Adenosine-Mediated Chronotropic Effects

Ying Fu, Xinyan Huang, Huailing Zhong, Richard M. Mortensen, Louis G. D’Alecy, and Richard R. Neubig
Circ. Res. 2006 98: 659-666. [Abstract] [Full Text] [PDF]