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

Ya Yu Chuang, Aline Valster, Salvatore J. Coniglio, Jonathan M. Backer, Marc Symons

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1927-1934
Number of pages8
JournalJournal of Cell Science
Volume120
Issue number11
DOIs
StatePublished - Jun 1 2007

Fingerprint

rho GTP-Binding Proteins
Focal Adhesions
Cell Movement
Myosin Light Chains
Guanine Nucleotides
GTP Phosphohydrolases
Guanosine Triphosphate
Wound Healing
Small Interfering RNA
Phosphorylation
Pharmacology
Genes

Keywords

  • Cell migration
  • Focal adhesion
  • Myosin
  • Rho
  • Wrch-1

ASJC Scopus subject areas

  • Cell Biology

Cite this

The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration. / Chuang, Ya Yu; Valster, Aline; Coniglio, Salvatore J.; Backer, Jonathan M.; Symons, Marc.

In: Journal of Cell Science, Vol. 120, No. 11, 01.06.2007, p. 1927-1934.

Research output: Contribution to journalArticle

Chuang, Ya Yu ; Valster, Aline ; Coniglio, Salvatore J. ; Backer, Jonathan M. ; Symons, Marc. / The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration. In: Journal of Cell Science. 2007 ; Vol. 120, No. 11. pp. 1927-1934.
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