The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

被引：489

作者：

de Lau, Wim ^{[1
]}

Peng, Weng Chuan ^{[2
]}

Gros, Piet ^{[2
]}

Clevers, Hans ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Univ Utrecht, Fac Sci, Dept Chem, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands

来源：

GENES & DEVELOPMENT | 2014年 / 28卷 / 04期

基金：

欧洲研究理事会;

关键词：

Lgr5; Rnf43/Znrf3; Rspondin; Wnt signal regulation; PROTEIN-COUPLED RECEPTOR; LEUCINE-RICH REPEAT; HUMAN HEPATOCELLULAR CARCINOMAS; POSTNATAL MAMMARY-GLAND; BETA-CATENIN MUTATIONS; R-SPONDIN RECOGNITION; EPITHELIAL STEM-CELL; HIGH-AFFINITY LIGAND; IN-VITRO EXPANSION; WNT/BETA-CATENIN;

D O I：

10.1101/gad.235473.113

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists.

引用

页码：305 / 316

页数：12

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