Article abstract


Nature Structural & Molecular Biology 14, 484 - 492 (2007)
Published online: 27 May 2007 | doi:10.1038/nsmb1247

The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization

Thomas Schwarz-Romond1,4,5, Marc Fiedler1,5, Naoki Shibata2,5, P Jonathan G Butler1, Akira Kikuchi3, Yoshiki Higuchi2 & Mariann Bienz1


The Wnt signaling pathway controls numerous cell fates in animal development and is also a major cancer pathway. Dishevelled (Dvl) transduces the Wnt signal by interacting with the cytoplasmic Axin complex. Dvl and Axin each contain a DIX domain whose molecular properties and structure are unknown. Here, we demonstrate that the DIX domain of Dvl2 mediates dynamic polymerization, which is essential for the signaling activity of Dvl2. The purified domain polymerizes gradually, reversibly and in a concentration dependent manner, ultimately forming fibrils. The Axin DIX domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal. The DIX domain thus seems to mediate the formation of a dynamic interaction platform with a high local concentration of binding sites for transient Wnt signaling partners; this represents a previously uncharacterized mechanistic principle, signaling by reversible polymerization.

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  1. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
  2. Department of Life Science, Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan and The RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5248, Japan.
  3. Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
  4. Present address: European Molecular Biology Organization, Meyerhofstr. 1, 69117 Heidelberg, Germany.
  5. These authors contributed equally to this work.

Correspondence to: Mariann Bienz1 e-mail: mb2@mrc-lmb.cam.ac.uk

Correspondence to: Yoshiki Higuchi2 e-mail: hig@sci.u-hyogo.ac.jp



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