leucine-rich repeats-containing G protein-coupled receptor 6, the class A of 7-transmembrane GPCRs
The leucine-rich repeat containing G-protein coupled receptor LGR5, together with its family members LGR4 and LGR6, is structurally related to the glycoprotein hormone receptor family, which includes the luteinizing hormone (LH) receptor, the follicle-stimulating hormone (FSH) receptor, and the pituitary thyroid-stimulating hormone (TSH) receptor. LGR4-6 are receptors for the R-spondin (Rspo) family of secreted proteins containing two N-terminal furin-like repeats and a thrombospondin domain. The Rspo proteins are involved in regulating proliferation and differentiation of adult stem cells by potently enhancing the WNT-stimulated beta-catenin signaling. LGR5 serves as a marker for resident stem cell in numerous epithelial cell layers, including small intestine, colon, stomach, and kidney. LGR6 is a marker for multipotent stem cells in the hair follicle that generate all skin cell lineages. In addition, LGR4 is broadly expressed in proliferating cells, and its deficient mice display development defects in multiple organs. Members of this group are characterized by a very large extracellular N-terminal domain containing 17 leucine-rich repeats (LRRs), flanked by cysteine-rich N- and C-terminal capping domains, and the extracellular domain is responsible for high-affinity binding with the Rspo proteins.