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.
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht, 3584 CT Utrecht, The Netherlands;
authors.forename: Wim
authors.initials: W
authors.lastname: de Lau
authors.forename: Weng Chuan
authors.initials: WC
authors.lastname: Peng
authors.forename: Piet
authors.initials: P
authors.lastname: Gros
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins; D044767:Ubiquitin-Protein Ligases
keywords: Lgr5; Rnf43/Znrf3; Rspondin; Wnt signal regulation