期刊
GENES & DEVELOPMENT
卷 28, 期 4, 页码 305-316出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.235473.113
关键词
Lgr5; Rnf43/Znrf3; Rspondin; Wnt signal regulation
资金
- EU [601876]
- EU ERC StemCellMark grant [232814]
- CancerGenomics.nl program of the Ministerie van Onderwijs, Cultuur, en Wetenschap (OCW)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek Spinoza grant [01.80.104.00]
- European Research Council (ERC) [232814] Funding Source: European Research Council (ERC)
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.
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