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LDL-receptor-related proteins in Wnt signal transduction

Author

Listed:
  • Keiko Tamai

    (Children's Hospital, Harvard Medical School)

  • Mikhail Semenov

    (Children's Hospital, Harvard Medical School)

  • Yoichi Kato

    (Children's Hospital, Harvard Medical School)

  • Rebecca Spokony

    (School of Veterinary Medicine, University of Pennsylvania)

  • Chunming Liu

    (Children's Hospital, Harvard Medical School)

  • Yu Katsuyama

    (Children's Hospital, Harvard Medical School)

  • Fred Hess

    (Merck Research Laboratories)

  • Jean-Pierre Saint-Jeannet

    (School of Veterinary Medicine, University of Pennsylvania)

  • Xi He

    (Children's Hospital, Harvard Medical School)

Abstract

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation1. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors2,3,4,5,6,7,8,9,10, but how Fz proteins transduce signalling is not understood. In Drosophila , arrow phenocopies the wingless (DWnt-1) phenotype11, and encodes a transmembrane protein11 that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12,13,14, 15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction. In Xenopus embryos, LRP6 activated Wnt–Fz signalling, and induced Wnt responsive genes, dorsal axis duplication and neural crest formation. An LRP6 mutant lacking the carboxyl intracellular domain blocked signalling by Wnt or Wnt–Fz, but not by Dishevelled or β-catenin, and inhibited neural crest development. The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex.

Suggested Citation

  • Keiko Tamai & Mikhail Semenov & Yoichi Kato & Rebecca Spokony & Chunming Liu & Yu Katsuyama & Fred Hess & Jean-Pierre Saint-Jeannet & Xi He, 2000. "LDL-receptor-related proteins in Wnt signal transduction," Nature, Nature, vol. 407(6803), pages 530-535, September.
    • Handle: RePEc:nat:nature:v:407:y:2000:i:6803:d:10.1038_35035117
    DOI: 10.1038/35035117
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    Cited by:

    1. Gili Hochman & Karin Halevi-Tobias & Yuri Kogan & Zvia Agur, 2017. "Extracellular inhibitors can attenuate tumorigenic Wnt pathway activity in adenomatous polyposis coli mutants: Predictions of a validated mathematical model," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-23, July.

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