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J. Biol. Chem. 282 (33): 24092-24098

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

Shuttling of G Protein Subunits between the Plasma Membrane and Intracellular Membranes*


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

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

Abstract: Heterotrimeric G proteins ({alpha}beta{gamma}) mediate the majority of signaling pathways in mammalian cells. It is long held that G protein function is localized to the plasma membrane. Here we examined the spatiotemporal dynamics of G protein localization using fluorescence recovery after photobleaching, fluorescence loss in photobleaching, and a photoswitchable fluorescent protein, Dronpa. Unexpectedly, G protein subunits shuttle rapidly (t1/2 < 1 min) between the plasma membrane and intracellular membranes. We show that consistent with such shuttling, G proteins constitutively reside in endomembranes. Furthermore, we show that shuttling is inhibited by 2-bromopalmitate. Thus, contrary to present thought, G proteins do not reside permanently on the plasma membrane but are constantly testing the cytoplasmic surfaces of the plasma membrane and endomembranes to maintain G protein pools in intracellular membranes to establish direct communication between receptors and endomembranes.

Received for publication May 23, 2007. Revision received June 7, 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.


The on-line version of this article (available at contain supplemental Figs. 1–9.

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}

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