LGR5 (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5) is a Protein Coding gene. Diseases associated with LGR5 include skin squamous cell carcinoma and colonic benign neoplasm. Among its related pathways are Signaling by GPCR and Wnt Signaling Pathways: beta-Catenin-independent Wnt/PCP Signaling Pathways. GO annotations related to this gene include G-protein coupled receptor activity and transmembrane signaling receptor activity. An important paralog of this gene is TSHR. The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene.
Orphan receptor. Stem cell marker of the intestinal epithelium and the hair follicule. Target gene of Wnt signaling. Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) also known as G-protein coupled receptor 49 (GPR49) or G-protein coupled receptor 67 (GPR67) is a protein that in humans is encoded by the LGR5 gene. It is a member of GPCR class A orphan receptor proteins. LGR5 is expressed across a diverse range of tissue such as in the muscle, placenta, spinal cord and brain and particularly as a biomarker of adult stem cells in certain tissues. LGR5 is a member of the Wnt signaling pathway. Although its ligand remains elusive, it has been shown that costimulation with R-spondin 1 and Wnt-3a induce increased internalization of LGR5. LGR5 also cointernalizes with LRP6 and FZD5 via a clathrin-dependent pathway to form a ternary complex upon Wnt ligand binding. Moreover, the rapid cointernalization of LRP6 by LGR5 induces faster rates of degradation for the former. It has been shown that the C-terminal region of LGR5 is crucial for both dynamic internalization and degradation to occur, although C-terminal truncation does not inhibit LRP6 interaction and internalization, but rather, heightens receptor activity. Thus, only the initial interaction with its unknown ligand and other membrane bound receptors is crucial in its role in Wnt signalling and not the internalization itself. LGR5 is crucial during embryogenesis as LGR null studies in mice incurred 100% neonatal mortality accompanied by several craniofacial distortions such as ankyloglossia and gastrointestinal dilation.