LGR6

LGR6 stands for leucine-rich repeat-containing G protein-coupled receptor 6. It encodes a member of the LGR family of GPCRs, which are characterized by an extracellular domain rich in leucine repeats and a seven-transmembrane region.

LGR6 binds the RSPO family of secreted proteins; RSPO1-4 interact with LGR4-6 to potentiate Wnt/β-catenin signaling. This potentiation largely occurs through inhibition of the ZNRF3 and RNF43 E3 ubiquitin ligases, which normally promote the degradation of Frizzled receptors, thereby increasing cellular responsiveness to Wnt ligands. The signaling role of LGR6 is considered to be primarily through modulation of the Wnt pathway rather than classic G protein signaling, though the exact G protein coupling is not fully resolved.

Expression of LGR6 is detected in multiple tissues, with notable presence in the skin. In the skin, LGR6 marks stem cells located in the hair follicle bulge and integrating into sebaceous glands. LGR6-positive cells function as epidermal stem cells capable of generating lineages that include hair follicles, sebaceous glands, and portions of the interfollicular epidermis, contributing to tissue regeneration and wound repair.

Research on LGR6 positions it as a marker of stem cell populations and as a modulator of Wnt signaling in normal physiology and disease. Its role makes it of interest in studies of tissue regeneration, stem cell biology, and cancers where Wnt signaling and stem cell-like properties are involved.