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J. Biol. Chem. 285 (6): 3905-3915

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Regulation of Phospholipase C-β2 Activity and Membrane Interaction by G{alpha}q, Gβ1{gamma}2, and Rac2*

Orit Gutman{ddagger}1, Claudia Walliser§1, Thomas Piechulek§, Peter Gierschik§21, , and Yoav I. Henis{ddagger}31

From the {ddagger}Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel, and
the §Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert-Einstein-Allee 11, 89081 Ulm, Germany

ABSTRACT Back to Top

Abstract: We combined fluorescence recovery after photobleaching (FRAP) beam-size analysis with biochemical assays to investigate the mechanisms of membrane recruitment and activation of phospholipase C-β2 (PLCβ2) by G protein {alpha}q and β{gamma} dimers. We show that activation by {alpha}q and β{gamma} differ from activation by Rac2 and from each other. Stimulation by {alpha}q enhanced the plasma membrane association of PLCβ2, but not of PLCβ2{Delta}, which lacks the {alpha}q-interacting region. Although {alpha}q resembled Rac2 in increasing the contribution of exchange to the FRAP of PLCβ2 and in enhancing its membrane association, the latter effect was weaker than with Rac2. Moreover, the membrane recruitment of PLCβ2 by {alpha}q occurred by enhancing PLCβ2 association with fast-diffusing (lipid-like) membrane components, whereas stimulation by Rac2 led to interactions with slow diffusing membrane sites. On the other hand, activation by β{gamma} shifted the FRAP of PLCβ2 and PLCβ2{Delta} to pure lateral diffusion 3- to 5-fold faster than lipids, suggesting surfing-like diffusion along the membrane. We propose that these different modes of PLCβ2 membrane recruitment may accommodate contrasting functional needs to hydrolyze phosphatidylinositol 4,5-bisphosphate (PtdInsP2) in localized versus dispersed populations. PLCβ2 activation by Rac2, which leads to slow lateral diffusion and much faster exchange, recruits PLCβ2 to act locally on PtdInsP2 at specific domains. Activation by {alpha}q leads to lipid-like diffusion of PLCβ2 accompanied by exchange, enabling the sampling of larger, yet limited, areas prior to dissociation. Finally, activation by β{gamma} recruits PLCβ2 to the membrane by transient interactions, leading to fast "surfing" diffusion along the membrane, sampling large regions for dispersed PtdInsP2 populations.

Key Words: G Proteins • Heterotrimeric G Proteins • Membrane Biophysics • Membrane Lipids • Phospholipase C • FRAP • Lateral Diffusion • Rac

Received for publication November 13, 2009.


1 These authors contributed equally to this work.

2 To whom correspondence may be addressed. Tel.: 49-731-5006-5500; Fax: 49-731-5006-5502; E-mail: peter.gierschik{at}

3 An incumbent of the Zalman Weinberg Chair in Cell Biology. To whom correspondence may be addressed. Tel.: 972-3-640-9053; Fax: 972-3-640-7643; E-mail: henis{at}

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