Premium
LGR4 and LGR5 are R‐spondin receptors mediating Wnt/β‐catenin and Wnt/PCP signalling
Author(s) -
Glinka Andrei,
Dolde Christine,
Kirsch Nadine,
Huang YaLin,
Kazanskaya Olga,
Ingelfinger Dierk,
Boutros Michael,
Cruciat CristinaMaria,
Niehrs Christof
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.175
Subject(s) - wnt signaling pathway , lgr5 , microbiology and biotechnology , lrp6 , biology , lrp5 , internalization , receptor , xenopus , signal transduction , biochemistry , gene
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.