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

by Huang, Ya‐Lin , Kirsch, Nadine , Niehrs, Christof , Dolde, Christine , Kazanskaya, Olga , Glinka, Andrei , Ingelfinger, Dierk , Cruciat, Cristina‐Maria , Boutros, Michael

in Animals / Catenin / Caveolin / Cell Line / Cell proliferation / Clathrin / Clathrin - metabolism / EMBO11 / EMBO37 / Embryo cells / Embryogenesis / Endocytosis / Furin / Gene Expression Regulation / HEK293 Cells / Hep G2 Cells / Humans / Internalization / LGR4 / LGR5 / Mammalian cells / Mice / Pattern formation / Protein Binding / R-spondin / Receptors / Receptors, G-Protein-Coupled - genetics / Receptors, G-Protein-Coupled - metabolism / Scientific Report / Scientific Reports / Stem cells / Thrombospondins - metabolism / Wnt / Wnt protein / Wnt Signaling Pathway / Xenopus / Xenopus - genetics / Xenopus - metabolism / Xenopus Proteins - genetics / Xenopus Proteins - metabolism

2011

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

by Huang, Ya‐Lin , Kirsch, Nadine , Niehrs, Christof , Dolde, Christine , Kazanskaya, Olga , Glinka, Andrei , Ingelfinger, Dierk , Cruciat, Cristina‐Maria , Boutros, Michael

2011

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

by Huang, Ya‐Lin , Kirsch, Nadine , Niehrs, Christof , Dolde, Christine , Kazanskaya, Olga , Glinka, Andrei , Ingelfinger, Dierk , Cruciat, Cristina‐Maria , Boutros, Michael

2011

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Journal Article

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

Huang, Ya‐Lin,

Kirsch, Nadine,

Niehrs, Christof,

Dolde, Christine,

Kazanskaya, Olga,

Glinka, Andrei,

Ingelfinger, Dierk,

Cruciat, Cristina‐Maria,

Boutros, Michael

2011

Overview

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. R‐spondins are secreted proteins known to synergize with Wnt signalling. The authors now show that R‐spondins are ligands for LGR4 and LGR5 orphan G‐protein‐coupled receptors. Binding of R‐spondins to LGRs positively regulates both Wnt/ ‐catenin and Wnt/PCP signalling pathways in vivo.

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Publisher

John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group

Subject

/ Catenin

/ Clathrin - metabolism