Mechanism of activation of the Formin protein Daam1

Wei Liu, Akira Sato, Deepak Khadka, Ritu Bharti, Hector Diaz, Loren W. Runnels, Raymond Habas

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The Formin proteins are central players in mediating cytoskeletal reorganization and are epistatically positioned in a pathway downstream of Rho activation. These proteins exist in the cytoplasm in an autoinhibited state, which is mediated by intramolecular interactions between the amino-terminal GTPase binding domain (GBD) that encompasses the diaphanous inhibitory domain (DID) and the carboxyl-terminal diaphanous autoregulatory domain (DAD). It has been proposed that the binding of Rho within the GBD releases this molecule from autoinhibition by disrupting the DID/DAD interactions. Here we report that Daam1 is not significantly activated by Rho binding but rather by its interaction with Dishevelled (Dvl). Removal of the DAD domain disrupts interactions between Dvl and Daam1, and the binding of Dvl to Daam1 disrupts the interaction between the GBD and DAD that mediates Daam1 autoinhibition. Mutations within or removal of the DAD converts Daam1 into an active protein that can induce Rho activation. We further demonstrate that Dvl synergizes with Daam1 to regulate gastrulation during Xenopus embryogenesis and that expression of activated Daam1 can rescue impaired convergent extension movements resulting from deregulated noncanonical Wnt signaling. Our studies together define the importance of a carboxyl-terminal binding partner, Dvl, that leads to the activation of Daam1.

Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number1
DOIs
Publication statusPublished - 8 Jan 2008
Externally publishedYes

Fingerprint

GTP Phosphohydrolases
rho GTP-Binding Proteins
Gastrulation
Proteins
Xenopus
Embryonic Development
Cytoplasm
Mutation

Keywords

  • Dishevelled
  • Rho
  • Wnt

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mechanism of activation of the Formin protein Daam1. / Liu, Wei; Sato, Akira; Khadka, Deepak; Bharti, Ritu; Diaz, Hector; Runnels, Loren W.; Habas, Raymond.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 1, 08.01.2008, p. 210-215.

Research output: Contribution to journalArticle

Liu, Wei ; Sato, Akira ; Khadka, Deepak ; Bharti, Ritu ; Diaz, Hector ; Runnels, Loren W. ; Habas, Raymond. / Mechanism of activation of the Formin protein Daam1. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 1. pp. 210-215.
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