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J. Biol. Chem. 282 (33): 24099-24108

© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

A Family of G Protein beta{gamma} Subunits Translocate Reversibly from the Plasma Membrane to Endomembranes on Receptor Activation*

Formula

Deepak Kumar Saini{ddagger}, Vani Kalyanaraman{ddagger}, Mariangela Chisari{ddagger}, , and Narasimhan Gautam{ddagger}§1

{ddagger}Department of Anesthesiology and §Genetics, Washington University School of Medicine, St. Louis, Missouri 63110

Abstract: The present model of G protein activation by G protein-coupled receptors exclusively localizes their activation and function to the plasma membrane (PM). Observation of the spatiotemporal response of G protein subunits in a living cell to receptor activation showed that 6 of the 12 members of the G protein {gamma} subunit family translocate specifically from the PM to endomembranes. The {gamma} subunits translocate as beta{gamma} complexes, whereas the {alpha} subunit is retained on the PM. Depending on the {gamma} subunit, translocation occurs predominantly to the Golgi complex or the endoplasmic reticulum. The rate of translocation also varies with the {gamma} subunit type. Different {gamma} subunits, thus, confer distinct spatiotemporal properties to translocation. A striking relationship exists between the amino acid sequences of various {gamma} subunits and their translocation properties. {gamma} subunits with similar translocation properties are more closely related to each other. Consistent with this relationship, introducing residues conserved in translocating subunits into a non-translocating subunit results in a gain of function. Inhibitors of vesicle-mediated trafficking and palmitoylation suggest that translocation is diffusion-mediated and controlled by acylation similar to the shuttling of G protein subunits (Chisari, M., Saini, D. K., Kalyanaraman, V., and Gautam, N. (2007) J. Biol. Chem. 282, 24092–24098). These results suggest that the continual testing of cytosolic surfaces of cell membranes by G protein subunits facilitates an activated cell surface receptor to direct potentially active G protein beta{gamma} subunits to intracellular membranes.


Received for publication February 8, 2007. Revision received April 13, 2007.

* This work was supported by National Institutes of Health Grant GM 69027 and an American Heart Association post-doctoral fellowship (to M. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


Formula

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–6 and Notes.

1 To whom correspondence should be addressed: Box 8054, Washington University School of Medicine, St. Louis, MO 63110. Tel.: 314-362 8568; Fax: 314-362-8571; E-mail: gautam{at}wustl.edu.


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