Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht, 3584 CT Utrecht, The Netherlands;
Genes Dev. 2014 Feb 15;28(4):305-16. doi: 10.1101/gad.235473.113.
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.
Lgr5 最初被发现是成年肠道隐窝和结肠癌中常见的 Wnt 靶基因。随后，它被确定为多种 Wnt 驱动的成年干细胞类型的精细标志物。Lgr5 及其同源物 Lgr4 和 Lgr6 构成了 R-spondins 的受体，R-spondins 是有效的 Wnt 信号增强子和干细胞生长因子。Lgr5/R-spondin 复合物通过中和 Rnf43 和 Znrf3 起作用，这两种跨膜 E3 连接酶将 Wnt 受体从干细胞表面去除。Rnf43/Znrf3 本身由 Wnt 靶基因编码，构成了负 Wnt 反馈环。因此，成年干细胞受到有效 Wnt 激动剂、拮抗剂和抗拮抗剂之间复杂的相互作用的控制。
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