Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1.
Wnt signaling via the Frizzled (Fz) receptor controls cell polarity and movement during development, but the molecular nature of Wnt/Fz polarity signal transduction remains poorly defined. Here we report that in human cells and during Xenopus embryogenesis, Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture. Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled (Dvl) and a novel Formin homology protein Daam1. Daam1 binds to both Dvl and Rho, and mediates Wnt-induced Dvl-Rho complex formation. Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta-catenin signaling. Our study illustrates a molecular pathway from Wnt/Fz signaling to Rho activation in cell polarity signal transduction.
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Division of Neuroscience, Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
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D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D051157:Frizzled Receptors; D005775:Gastrula / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins; D009687:Nuclear Proteins / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology / Q000502:physiology*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C499094:DAAM1 protein, human; C443939:Daam1 protein, Xenopus; D051157:Frizzled Receptors; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D020741:rho GTP-Binding Proteins