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Genes to Cells (2009) 14, 1197-1207. doi:10.1111/j.1365-2443.2009.01345.x
© 2009 Blackwell Publishing or its licensors
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DIP/WISH-deficient mice reveal Dia- and N-WASP-interacting protein as a regulator of cytoskeletal dynamics in embryonic fibroblasts

 Tomoko Fukumi-Tominaga1,2,3,*, Yoshiko Mori4, Atsuko Matsuura1,2, Keiko Kaneko1,2, Makoto Matsui1,2, Masato Ogata4 and Makoto Tominaga1,2,3

1 Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan
2 National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki 444-8585, Japan
3 Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan
4 Department of Biochemistry, Faculty of Medicine, Mie University, Tsu 514-8507, Japan

DIP/WISH binds to mammalian diaphanous and N-WASP, and functions as a scaffold protein by binding to Nck protein (called SPIN90). In addition, DIP/WISH accelerates actin polymerization through integration with N-WASP and is involved in cytoskeletal dynamics. We previously reported that DIP controls the activities of Rho GTPases in a Src-dependent manner, and accordingly contributes to cell motility (Meng et al. 2004). Here, we made the mice lacking DIP/WISH and demonstrated that DIP/WISH is critical for cell motility and adhesion by using murine embryonic fibroblasts (MEF). Rho activity was higher in DIP/WISH-deficient MEF cells even before platelet-derived growth factor (PDGF) or adhesion stimulation. Cell motility and adhesion were impaired in DIP/WISH-deficient MEF cells, and the MEF cells moved little probably due to the deficiency of tail retractions although they had many small membrane ruffles. Consistent with high Rho activity, DIP/WISH-deficient MEF cells exhibited many stress fibers due to clustering pre-existing actin filament. Thus, DIP/WISH is a negative regulator of Rho and modulates cell adhesion by controlling the integration of adhesion molecules.

Communicated by: Yo-ichi Nabeshima

* ttfukumi{at}hotmail.com






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