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

被引：454
作者：
Glinka, Andrei [1 ]
Dolde, Christine [1 ]
Kirsch, Nadine [1 ]
Huang, Ya-Lin [1 ]
Kazanskaya, Olga [1 ]
Ingelfinger, Dierk [2 ,3 ]
Boutros, Michael [2 ,3 ]
Cruciat, Cristina-Maria [1 ]
Niehrs, Christof [1 ,4 ]
机构：
[1] DKFZ, DKFZ ZMBH Alliance, Div Mol Embryol, D-69120 Heidelberg, Germany
[2] DKFZ, Div Signalling & Funct Genom, D-69120 Heidelberg, Germany
[3] Univ Heidelberg, D-69120 Heidelberg, Germany
[4] Inst Mol Biol, D-55128 Mainz, Germany
来源：
EMBO REPORTS | 2011年 / 12卷 / 10期
关键词：
endocytosis; LGR4; LGR5; R-spondin; Wnt; STEM-CELLS; WNT; R-SPONDIN1; LRP6; DIFFERENTIATION; ENDOCYTOSIS; LIGANDS; PATHWAY; DISEASE; XENOPUS;
D O I：
10.1038/embor.2011.175
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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/beta-catenin and Wnt/PCP signalling. R-spondin-triggered beta-catenin signalling requires Clathrin, while Wnt3a-mediated beta-catenin signalling requires Caveolin-mediated endocytosis, suggesting that internalization has a mechanistic role in R-spondin signalling.
引用
收藏
页码：1055 / 1061
页数：7
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