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EMBO Rep. 2011 Sep 30;12(10):1055-61. doi: 10.1038/embor.2011.175.

LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling.

Author information

1
Division of Molecular Embryology, DKFZ-ZMBH Alliance, DKFZ, Im Neuenheimer Feld 580, Heidelberg D-69120, Germany.

Abstract

R-spondins are secreted Wnt signalling agonists, which regulate embryonic patterning and stem cell proliferation, but whose mechanism of action is poorly understood. Here we show that R-spondins bind to the orphan G-protein-coupled receptors LGR4 and LGR5 by their Furin domains. Gain- and loss-of-function experiments in mammalian cells and Xenopus embryos indicate that LGR4 and LGR5 promote R-spondin-mediated Wnt/β-catenin and Wnt/PCP signalling. R-spondin-triggered β-catenin signalling requires Clathrin, while Wnt3a-mediated β-catenin signalling requires Caveolin-mediated endocytosis, suggesting that internalization has a mechanistic role in R-spondin signalling.

PMID:
21909076
PMCID:
PMC3185347
DOI:
10.1038/embor.2011.175
[Indexed for MEDLINE]
Free PMC Article

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