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

被引：461

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

页码：1055 / 1061

页数：7

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