LGR5
Description
The LGR5 (leucine rich repeat containing G protein-coupled receptor 5) is a protein-coding gene located on chromosome 12.
LGR5, also known as G-protein coupled receptor 49 (GPR49) or G-protein coupled receptor 67 (GPR67), is a protein encoded by the LGR5 gene in humans. It is classified as a member of GPCR class A receptor proteins. R-spondin proteins are the biological ligands of LGR5. LGR5 is expressed in a variety of tissues including muscle, placenta, spinal cord, and brain, and is particularly known as a biomarker of adult stem cells in certain tissues. Before its current designation, LGR5 was also referred to as FEX, HG38, GPR49, and GPR67. The human LGR5 gene spans 144,810 bases and resides on chromosome 12 at position 12q22-q23. Both human, rat, and mouse homologs contain 907 amino acids and seven transmembrane domains. After translation, the signal peptide (amino acids 1-21) is removed, and the mature peptide (amino acids 22-907) inserts its transmembrane domain into the translocon membrane before being packaged towards the plasma membrane. LGR5 exhibits high conservation within the mammalian clade. Sequence analysis revealed that the transmembrane regions and cysteine-flanked junction between TM1 and the extracellular domain are highly conserved across various species, including sea anemone, fly, worm, snail, rat, and human.
LGR5 acts as a receptor for R-spondins, enhancing the canonical Wnt signaling pathway and serving as a stem cell marker in the intestinal epithelium and hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3, or RSPO4), LGR5 interacts with phosphorylated LRP6 and frizzled receptors, which are activated by extracellular Wnt receptors. This interaction triggers the canonical Wnt signaling pathway, leading to increased expression of target genes. Notably, LGR5 does not activate heterotrimeric G-proteins for signal transduction, unlike typical G-protein coupled receptors. LGR5 plays a crucial role in the development and maintenance of adult intestinal stem cells during postembryonic development. It is found in a complex alongside RNF43, RSPO1, and itself (LGR5). LGR5 also interacts with other R-spondin ligands, including RSPO2, RSPO3, and RSPO4.
LGR5 is also known as FEX, GPR49, GPR67, GRP49, HG38.
