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A Family of G Protein βγ Subunits Translocate Reversibly from the Plasma Membrane to Endomembranes on Receptor Activation

J. Biol. Chem., 17 August 2007
Vol. 282, Issue 33, p. 24099-24108
DOI: 10.1074/jbc.M701191200

A Family of G Protein βγ Subunits Translocate Reversibly from the Plasma Membrane to Endomembranes on Receptor Activation

  1. Deepak Kumar Saini ,
  2. Vani Kalyanaraman ,
  3. Mariangela Chisari and
  4. Narasimhan Gautam § 1
  1. Department of Anesthesiology and §Genetics, Washington University School of Medicine, St. Louis, Missouri 63110
  1. 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}


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 γ subunit family translocate specifically from the PM to endomembranes. The γ subunits translocate as βγ complexes, whereas the α subunit is retained on the PM. Depending on the γ subunit, translocation occurs predominantly to the Golgi complex or the endoplasmic reticulum. The rate of translocation also varies with the γ subunit type. Different γ subunits, thus, confer distinct spatiotemporal properties to translocation. A striking relationship exists between the amino acid sequences of various γ subunits and their translocation properties. γ 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 βγ subunits to intracellular membranes.


  • 2 The abbreviations used are: GPCR, G protein-coupled receptor; PM, plasma membrane; FRET, fluorescence resonance energy transfer; CHO, Chinese hamster ovary; ER, endoplasmic reticulum; CFP, cyan fluorescent protein; YFP, yellow fluorescent protein; 2BP, 2-bromopalmitate; mCh, mCherry.

  • * 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.

  • Embedded Image The on-line version of this article (available at contains supplemental Figs. 1–6 and Notes.

    • Received February 8, 2007.
    • Revision received April 13, 2007.


D. K. Saini, V. Kalyanaraman, M. Chisari, and N. Gautam, A Family of G Protein βγ Subunits Translocate Reversibly from the Plasma Membrane to Endomembranes on Receptor Activation. J. Biol. Chem. 282, 24099-24108 (2007).

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