Hsu SY, et al 2000 reported the classification of three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR) and the identification of LGR6 and LGR7 and the signaling mechanism for LGR7.
Glycoprotein hormone receptors, including LH receptor, FSH receptor, and TSH
receptor, belong to the large G protein-coupled receptor (GPCR) superfamily but
are unique in having a large ectodomain important for ligand binding. The authors identified two new
paralogs, LGR6 and LGR7, for glycoprotein hormone receptors. Phylogenetic
analysis showed that there are three LGR subgroups: the known glycoprotein
hormone receptors; LGR4 to 6; and a third subgroup represented by LGR7. LGR6
has a subgroup-specific hinge region after leucine-rich repeats whereas LGR7,
like snail LGR, contains a low density lipoprotein (LDL) receptor cysteine-rich
motif at the N terminus. Similar to LGR4 and LGR5, LGR6 and LGR7 mRNAs are
expressed in multiple tissues, including the ovary. Although the putative ligands for LGR6 and LGR7
are unknown, studies on single amino acid mutants of LGR7, with a design based
on known LH and TSH receptor gain-of-function mutations, indicated that the
action of LGR7 is likely mediated by the protein kinase A but not the
phospholipase C pathway. Thus, mutagenesis of conserved residues to allow
constitutive receptor activation is a novel approach for the characterization of
signaling pathways of selective orphan GPCRs. The present study also defines the
existence of three subclasses of leucine-rich repeat-containing, G protein-coupled
receptors in the human genome and allows future studies on the physiological
importance of this expanding subgroup of GPCR.
NCBI Summary:
This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
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Expression regulated by
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Ovarian localization
Oocyte
Comment
Hsu SY, et al 2000 reported that LGR6 is present in the ovary detected by Northern blotting assay.
Follicle stages
Comment
Identification and developmental expression of leucine-rich repeat-containing G protein-coupled receptor 6 (lgr6) in the medaka fish, Oryzias latipes. Deguchi T et al. G protein-coupled receptors are critical regulators of diverse developmental processes such as oocyte maturation, fertilization, gastrulation, and organogenesis. To further study the molecular mechanisms underlying these processes, we cloned and characterized the orphan leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), a stem cell marker in mammalian hair follicles, in medaka fish, Oryzias latipes. To examine the expression pattern of lgr6, we performed whole-mount in situ hybridization (WISH) during embryogenesis. The expression of lgr6 was first detected as a band in the anterior part of the posterior brain vesicle in 0.5-1day post fertilization (dpf) embryos. This band disappeared by 2 dpf, but new signals appeared in the otic vesicles bordering the original band and also detected in the nasal placode and posterior lateral line primordia. At later stages (3-5 dpf), lgr6 was widely expressed in the brain, otic vesicle, neuromasts, root of the pectoral fin, cranial cartilage, and gut. Then, we conducted more detailed expression analysis of lgr6 in adult gut using WISH and immunohistochemical staining. Lgr6-positive cells were detected in the crypt-like proliferative zone and in parts of the villus. We also performed RT-PCR of mRNAs from different tissues. The lgr6 mRNA was found highest in the kidney and gill. The transcript was also present in the brain, heart, liver, spleen, intestine, skeletal muscle, testis, and ovary, similar to that of mammalian LGR6. These results suggest that medaka lgr6 plays an important role in organ development during embryogenesis and serves as a good molecular marker for future studies of postembryonic organ-specific development in mammals.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Snippert HJ et al. Mammalian epidermis consists of three self-renewing compartments: the hair follicle, the sebaceous gland, and the interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative of the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland, and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, whereas contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell. LGR6 KO mice are fertile.