The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration.
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.
Chuang
Ya-yu
YY
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, North Shore University Hospital, Manhasset, NY 11030, USA.
Valster
Aline
A
Coniglio
Salvatore J
SJ
Backer
Jonathan M
JM
Symons
Marc
M
D002465:Cell Movement; D004789:Enzyme Activation; D022001:Focal Adhesions / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*
D048031:JNK Mitogen-Activated Protein Kinases; D018994:Myosin Light Chains; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins; C515903:PAK1 protein, human; C432668:RHOU protein, human