Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 11 February 2003
Vol. 2003, Issue 169, p. tw61
[DOI: 10.1126/stke.2003.169.tw61]


G Proteins Setting Gβ{gamma} Free Without a Receptor

Rishal et al. have described a novel mode of heterotrimeric guanine nucleotide-binding protein (G protein) regulation that points to a possible role for Na+ as a second messenger. G protein-activated inward rectifier K+ channels (GIRKs) play a role in regulating the heartbeat and mediate the effects of many inhibitory neurotransmitters. These channels are activated by the G protein β{gamma} heterodimer (Gβ{gamma}), which is released from the heterotrimer after stimulation of G protein-coupled receptors (GPCRs) and GTP binding to the Gα subunit. GIRKs are also rapidly activated by intracellular Na+ independently of G proteins. Rishal et al. used inside-out patch clamp analysis to investigate activation of GIRK channels expressed in Xenopus oocytes. They observed a slow phase of Na+-dependent activation in both wild-type channels and mutant channels lacking fast Na+-dependent activation. Although slow Na+ activation of GIRK was inhibited by a protein that bound Gβ{gamma}, it did not require GTP in the medium. High Na+ reduced the association of radiolabeled Gβ{gamma} with a GDP-bound fusion protein of Gα with glutathione S-transferase (GST-GαGDP) and decreased Gβ{gamma} binding to GST-GαGDP as assessed by surface plasmon resonance. Mild overexpression of Gα (which should increase the fraction of total Gβ{gamma} bound to GαGDP) enhanced slow Na+-dependent activation of GIRK. These data suggest that Na+ regulates the resting equilibrium between free Gβ{gamma} and Gβ{gamma} bound to GαGDP and may, under some conditions, act as a second messenger coupling electrical activity in excitable cells to GPCR-independent effects of Gβ{gamma} on target proteins.

I. Rishal, T. Keren-Raifman, D. Yakubovich, T. Ivanina, C. W. Dessauer, V. Z. Slepak, N. Dascal, Na+ promotes the dissociation between GαGDP and Gβ{gamma}, activating G protein-gated K+ channels. J. Biol. Chem. 278, 3840-3845 (2003). [Abstract] [Full Text]

Citation: Setting Gβ{gamma} Free Without a Receptor. Sci. STKE 2003, tw61 (2003).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882