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

Wim de Lau; Weng Chuan Peng; Piet Gros; Hans Clevers

doi:10.1101/gad.235473.113

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

Wim de Lau, Weng Chuan Peng, Piet Gros, Hans Clevers

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

504 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	305-16
Aantal pagina's	12
Tijdschrift	Genes & Development
Volume	28
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1101/gad.235473.113
Status	Gepubliceerd - 15 feb. 2014

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title = "The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength",

abstract = "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.",

keywords = "Animals, Embryonic Development, Gene Expression Regulation, Humans, Receptors, G-Protein-Coupled, Signal Transduction, Thrombospondins, Ubiquitin-Protein Ligases, Wnt Signaling Pathway",

author = "{de Lau}, Wim and Peng, {Weng Chuan} and Piet Gros and Hans Clevers",

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AU - de Lau, Wim

AU - Peng, Weng Chuan

AU - Gros, Piet

AU - Clevers, Hans

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AB - 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.

KW - Animals

KW - Embryonic Development

KW - Gene Expression Regulation

KW - Humans

KW - Receptors, G-Protein-Coupled

KW - Signal Transduction

KW - Thrombospondins

KW - Ubiquitin-Protein Ligases

KW - Wnt Signaling Pathway

U2 - 10.1101/gad.235473.113

DO - 10.1101/gad.235473.113

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

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