LGR4 和 LGR5 是 R-spondin 受体，介导 Wnt/β-catenin 和 Wnt/PCP 信号通路。
LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling.
机构信息
Division of Molecular Embryology, DKFZ-ZMBH Alliance, DKFZ, Im Neuenheimer Feld 580, Heidelberg D-69120, Germany.
出版信息
EMBO Rep. 2011 Sep 30;12(10):1055-61. doi: 10.1038/embor.2011.175.
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.
摘要
R -spondins 是分泌型 Wnt 信号激动剂，可调节胚胎形态发生和干细胞增殖，但作用机制尚不清楚。本文中，作者发现 R-spondins 通过其 Furin 结构域与孤儿 G 蛋白偶联受体 LGR4 和 LGR5 结合。哺乳动物细胞和非洲爪蟾胚胎的功能获得和缺失实验表明，LGR4 和 LGR5 促进 R-spondin 介导的 Wnt/β-catenin 和 Wnt/PCP 信号转导。R-spondin 触发的 β-catenin 信号需要网格蛋白，而 Wnt3a 介导的 β-catenin 信号需要窖蛋白介导的内吞作用，提示内化在 R-spondin 信号中具有机械作用。
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