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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Carrier Proteins / physiology
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Cell Polarity / physiology*
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Embryo, Nonmammalian / physiology
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Frizzled Receptors
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Gastrula / physiology*
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Humans
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Microfilament Proteins
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Nuclear Proteins / physiology
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Proteins / physiology*
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Proto-Oncogene Proteins / physiology*
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Signal Transduction
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Wnt Proteins
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Xenopus / embryology
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Xenopus / physiology*
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Xenopus Proteins*
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Zebrafish Proteins*
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rho GTP-Binding Proteins / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DAAM1 protein, human
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Daam1 protein, Xenopus
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Frizzled Receptors
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Microfilament Proteins
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Nuclear Proteins
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Proteins
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Proto-Oncogene Proteins
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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rho GTP-Binding Proteins