title: LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling.
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.
authors: Division of Molecular Embryology, DKFZ-ZMBH Alliance, DKFZ, Im Neuenheimer Feld 580, Heidelberg D-69120, Germany.
authors: Andrei
authors: A
authors: Glinka
authors: Christine
authors: C
authors: Dolde
authors: Nadine
authors: N
authors: Kirsch
authors: Ya-Lin
authors: YL
authors: Huang
authors: Olga
authors: O
authors: Kazanskaya
authors: Dierk
authors: D
authors: Ingelfinger
authors: Michael
authors: M
authors: Boutros
authors: Cristina-Maria
authors: CM
authors: Cruciat
authors: Christof
authors: C
authors: Niehrs
mesh_terms: D000818:Animals; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D019699:Thrombospondins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D014981:Xenopus / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D000098907:R-Spondins
chemical_list: D002966:Clathrin; D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins; D029867:Xenopus Proteins; C116884:LGR5 protein, human; C475438:RSPO3 protein, human; D000098907:R-Spondins