LGR4 and LGR5 are R-spondin receptors mediating Wnt/?-catenin and Wnt/PCP signalling. uri icon

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/?-catenin and Wnt/PCP signalling. R-spondin-triggered ?-catenin signalling requires Clathrin, while Wnt3a-mediated ?-catenin signalling requires Caveolin-mediated endocytosis, suggesting that internalization has a mechanistic role in R-spondin signalling.

publication date

  • September 30, 2011