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First published online November 9, 2005
doi: 10.1242/10.1242/jcs.02640

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Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B

Guillaume Bompard^1,*, Stewart J. Sharp¹, Gilles Freiss² and Laura M. Machesky^1,

¹ School of Biosciences, Division of Molecular Cell Biology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
² Inserm U540, Endocrinologie Moléculaire et Cellulaire des Cancers, 60, rue de Navacelles, 34090 Montpellier, France

Author for correspondence (e-mail: l.m.machesky{at}bham.ac.uk)

Accepted 15 August 2005

Numerous scaffold proteins coordinate signals from the environment with actin-based protrusions during shape change and migration. Many scaffolds integrate signals from Rho-family GTPases to effect the assembly of specific actin structures. Here we investigate the mechanism of action MIM-B (missing in metastasis-B) on the actin cytoskeleton. MIM-B binds actin monomer through a WASP homology 2 motif, bundles actin filaments via an IRSp53/MIM domain, and is a long isoform of MIM, a proposed metastasis suppressor. We analysed the activity of MIM-B toward the actin cytoskeleton as well as its potential link to cancer metastasis. Endogenous MIM-B protein is widely expressed and its expression is maintained in various metastatic cell lines. MIM-B induces lamellipodia-like actin-rich protrusions. The IRSp53/MIM domain of MIM-B, as well as Rac activity are required to induce protrusions, but not the WASP homology 2 motif. MIM-B binds and activates Rac via its IRSp53/MIM domain, but this is not sufficient to induce lamellipodia. Finally, our data revealed that actin bundling and Rac-binding properties of MIM-B are not separable. Thus, MIM-B is unlikely to be a metastasis suppressor but acts as a scaffold protein that interacts with Rac, actin and actin-associated proteins to modulate lamellipodia formation.

Key words: Actin cytoskeleton, Lamellipodia, Rho GTPases, Rac, Bundling

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