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First published online 15 May 2007
doi: 10.1242/jcs.03456

Journal of Cell Science 120, 1927-1934 (2007)
Published by The Company of Biologists 2007
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Research Article

The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration

Ya-yu Chuang1,*, Aline Valster1,*,{ddagger}, Salvatore J. Coniglio1,2, Jonathan M. Backer3 and Marc Symons1,2,4,§

1 Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, North Shore University Hospital, Manhasset, NY 11030, USA
2 Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
4 Department of Surgery, North Shore University Hospital, Manhasset, NY 11030, USA

§ Author for correspondence (e-mail: msymons{at}nshs.edu)

Accepted 15 March 2007

Wrch-1 (Wnt-regulated Cdc42 homolog) is a new member of the Rho family that was identified as a gene transcriptionally upregulated by Wnt-1. Wrch-1 has no detectable GTPase activity and displays very high intrinsic guanine nucleotide exchange, implying that it is constitutively GTP-bound. The biological functions of Wrch-1 largely remain to be characterized. Here, we report that Wrch-1 prominently localizes to focal adhesions. Depletion of Wrch-1 by small interfering RNA increases focal adhesion formation, whereas Wrch-1 overexpression disassembles focal adhesions. Wrch-1 depletion inhibits myosin-light-chain phosphorylation, which in turn leads to an increase in the number of focal adhesions and inhibits cell migration in response to wound healing. Depletion of Wrch-1 also inhibits Akt and JNK activation. Although pharmacological inhibitors of Akt and JNK inhibit cell migration, they do not affect focal adhesions. Thus, our data suggest that Wrch-1 regulates cell migration by multiple mechanisms: on the one hand Wrch-1 controls focal adhesions by regulating myosin light chain and on the other hand Wrch-1 stimulates the activation of Akt and JNK.

Key words: Wrch-1, Rho, Focal adhesion, Cell migration, Myosin




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