WGEF activates Rho in the Wnt-PCP pathway and controls convergent extension in Xenopus gastrulation.
The Wnt-PCP (planar cell polarity, PCP) pathway regulates cell polarity and convergent extension movements during axis formation in vertebrates by activation of Rho and Rac, leading to the re-organization of the actin cytoskeleton. Rho and Rac activation require guanine nucleotide-exchange factors (GEFs), but the identity of the GEF involved in Wnt-PCP-mediated convergent extension is unknown. Here we report the identification of the weak-similarity GEF (WGEF) gene by a microarray-based screen for notochord enriched genes, and show that WGEF is involved in Wnt-regulated convergent extension. Overexpression of WGEF activated RhoA and rescued the suppression of convergent extension by dominant-negative Wnt-11, whereas depletion of WGEF led to suppression of convergent extension that could be rescued by RhoA or Rho-associated kinase activation. WGEF protein preferentially localized at the plasma membrane, and Frizzled-7 induced colocalization of Dishevelled and WGEF. WGEF protein can bind to Dishevelled and Daam-1, and deletion of the Dishevelled-binding domain generates a hyperactive from of WGEF. These results indicate that WGEF is a component of the Wnt-PCP pathway that connects Dishevelled to Rho activation.
Tanegashima
Kosuke
K
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Zhao
Hui
H
Dawid
Igor B
IB
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D000072261:Dishevelled Proteins; D054262:Gastrulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009672:Notochord / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D020662:Guanine Nucleotide Exchange Factors; D010750:Phosphoproteins; D051153:Wnt Proteins; D020741:rho GTP-Binding Proteins