Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1

Cell. 2001 Dec 28;107(7):843-54. doi: 10.1016/s0092-8674(01)00614-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins / physiology
  • Cell Polarity / physiology*
  • Embryo, Nonmammalian / physiology
  • Frizzled Receptors
  • Gastrula / physiology*
  • Humans
  • Nuclear Proteins / physiology
  • Proteins / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Signal Transduction
  • Wnt Proteins
  • Xenopus / embryology
  • Xenopus / physiology*
  • Xenopus Proteins*
  • Zebrafish Proteins*
  • rho GTP-Binding Proteins / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DAAM1 protein, human
  • Daam1 protein, Xenopus
  • Frizzled Receptors
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • rho GTP-Binding Proteins