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LDL-receptor-related proteins in Wnt signal transduction

Tamai, Keiko, Semenov, Mikhail, Kato, Yoichi, Spokony, Rebecca, Liu, Chunming, Katsuyama, Yu, Hess, Fred, Saint-Jeannet, Jean-Pierre, He, Xi·2000·Nature
DOI 10.1038/35035117
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Abstract

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors, but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype, and encodes a transmembrane protein that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). 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 beta-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.

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  • LRP6 can bind Wnt1, Wnt3a and Xenopus Wnt8.

    “By using co-immunoprecipitation, several group reported that LRP6 can bind Wnt1, Wnt3a and Xenopus Wnt8 (Tamai et al., 2000;Mao et al., 2001;Kato et al., 2002;Itasaki et al., 2003;Liu et al., 2003).”

    From Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding (2005) · cites this paper as Tamai et al., 2000

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Research works printed but not linked: 30

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Metadata

Authors
Tamai, K., Semenov, M., Kato, Y., Spokony, R., Liu, C., Katsuyama, Y., Hess, F., Saint-Jeannet, J.-P., & He, X.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2000-09
Volume
407
Issue
6803
Pages
530-535
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/35035117
Cited by
1,128
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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