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Vol. 18, Issue 12, 4780-4793, December 2007

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Interaction of Ezrin with the Novel Guanine Nucleotide Exchange Factor PLEKHG6 Promotes RhoG-dependent Apical Cytoskeleton Rearrangements in Epithelial Cells

Romina D'Angelo^*,, Sandra Aresta, Anne Blangy, Laurence Del Maestro^*,, Daniel Louvard^*,, and Monique Arpin^*,

*Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Paris 75248, France; Institut Curie, Centre de Recherche, Paris 75248, France; Hybrigenics, 75014 Paris, France; and Centre National de la Recherche Scientifique, Centre de Recherche de Biochimie Macromoléculaire, 34293 Montpellier Cedex 5, France

Submitted December 22, 2006; Revised July 18, 2006; Accepted September 11, 2007
Monitoring Editor: Martin A. Schwartz

The mechanisms underlying functional interactions between ERM (ezrin, radixin, moesin) proteins and Rho GTPases are not well understood. Here we characterized the interaction between ezrin and a novel Rho guanine nucleotide exchange factor, PLEKHG6. We show that ezrin recruits PLEKHG6 to the apical pole of epithelial cells where PLEKHG6 induces the formation of microvilli and membrane ruffles. These morphological changes are inhibited by dominant negative forms of RhoG. Indeed, we found that PLEKHG6 activates RhoG and to a much lesser extent Rac1. In addition we show that ezrin forms a complex with PLEKHG6 and RhoG. Furthermore, we detected a ternary complex between ezrin, PLEKHG6, and the RhoG effector ELMO. We demonstrate that PLEKHG6 and ezrin are both required in macropinocytosis. After down-regulation of either PLEKHG6 or ezrin expression, we observed an inhibition of dextran uptake in EGF-stimulated A431 cells. Altogether, our data indicate that ezrin allows the local activation of RhoG at the apical pole of epithelial cells by recruiting upstream and downstream regulators of RhoG and that both PLEKHG6 and ezrin are required for efficient macropinocytosis.

Address correspondence to: Monique Arpin (marpin{at}curie.fr).

Abbreviations used: DH, Dbl-homology; EGF, epidermal growth factor; ERM, ezrin, radixin, moesin; GDI, guanine dissociation inhibitor; GEF, guanine nucleotide exchange factor; GFP, green fluorescent protein; GST, glutathione S-transferase; PH, pleckstrin homology; PLEKHG6, pleckstrin homology domain containing, family G (with RhoGef domain) member 6; TRITC-dextran, tetramethylrhodamine isothiocyanate-dextran.

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