Alternative titles; symbols
HGNC Approved Gene Symbol: GPR3
Cytogenetic location: 1p36.11 Genomic coordinates (GRCh38): 1:27,392,622-27,395,814 (from NCBI)
In a search for genes responsible for the mediation of brain reward that may have a role in drug addiction, Marchese et al. (1994) cloned a gene designated GPR3 that showed 56% identity in the transmembrane regions with a previously characterized cDNA clone from rat.
Independently, Iismaa et al. (1994) used degenerate oligonucleotide primers designed against known G protein-coupled receptors and PCR amplification to isolate a novel receptor sequence from a rat insulinoma cell line and its human homolog, GPR3, from a human neuroblastoma cDNA library. The novel human receptor sequence was expressed in low abundance predominantly in the central nervous system and at low levels in lung and kidney.
By expressing GPR3 in a large variety of cell lines, Eggerickx et al. (1995) demonstrated that GPR3 activates adenylate cyclase to a level similar to that obtained with other Gs-coupled receptors that are fully stimulated by their ligands.
Mehlmann et al. (2004) demonstrated that GPR3 maintained meiotic arrest in mammalian oocytes. Oocytes from Gpr3 knockout mice resumed meiosis within antral follicles, independently of an increase in luteinizing hormone; this phenotype could be reversed by injection of Gpr3 RNA into the oocytes. Mehlmann et al. (2004) concluded that the GPR3 receptor is a link in communication between somatic cells and oocyte of the ovarian follicle and is crucial for the regulation of meiosis.
Using a high-throughput functional genomic screen, Thathiah et al. (2009) identified GPR3, a constitutively active G protein-coupled receptor, as a modulator of amyloid-beta (see 104760) production. Overexpression of GPR3 stimulated amyloid-beta production, whereas genetic ablation of GPR3 prevented accumulation of the amyloid-beta peptide in vitro and in an Alzheimer disease (see 104300) mouse model. GPR3 expression led to increased formation and cell surface localization of the mature gamma-secretase complex in the absence of an effect on Notch (see 190198) processing. GPR3 is highly expressed in areas of the normal human brain implicated in Alzheimer disease (Iismaa et al., 1994) and is elevated in the sporadic Alzheimer disease brain (Thathiah et al., 2009), which provides support for the involvement of GPR3 in Alzheimer disease.
Iismaa et al. (1994) showed that the GPR3 gene is intronless within the coding region, containing at least 1 intron in the 5-prime untranslated region.
Song et al. (1995) found that this receptor protein of 330 amino acids is encoded by a single exon.
Using FISH, Marchese et al. (1994) localized the GPR3 gene to chromosome 1p36.1-p35. Iismaa et al. (1994) mapped the GPR3 gene to chromosome 1p34.3 by FISH. Using FISH, Song et al. (1995) assigned the GPR3 gene to chromosome 1p36.1-p34.3.
In Gpr3-null mice, Ledent et al. (2005) observed progressive reduction in litter size despite a stable, age-independent alteration of the meiotic pause, characterized by premature resumption of meiosis in about one-third of antral follicles in Gpr3 -/- females regardless of age. Aging Gpr3-null mice had severe reduction of fertility, manifested by an increasing number of nondeveloping early embryos upon spontaneous ovulation and massive amounts of fragmented oocytes after superovulation. Ledent et al. (2005) concluded that GPR3 plays a role in the protection or rescue of oocytes from aging.
Eggerickx, D., Denef, J.-F., Labbe, O., Hayashi, Y., Refetoff, S., Vassart, G., Parmentier, M., Libert, F. Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase. Biochem. J. 309: 837-843, 1995. [PubMed: 7639700] [Full Text: https://doi.org/10.1042/bj3090837]
Iismaa, T. P., Kiefer, J., Liu, M. L., Baker, E., Sutherland, G. R., Shine, J. Isolation and chromosomal localization of a novel human G-protein-coupled receptor (GPR3) expressed predominantly in the central nervous system. Genomics 24: 391-394, 1994. [PubMed: 7698767] [Full Text: https://doi.org/10.1006/geno.1994.1635]
Ledent, C., Demeestere, I., Blum, D., Petermans, J., Hamalainen, T., Smits, G., Vassart, G. Premature ovarian aging in mice deficient for Gpr3. Proc. Nat. Acad. Sci. 102: 8922-8926, 2005. [PubMed: 15956199] [Full Text: https://doi.org/10.1073/pnas.0503840102]
Marchese, A., Docherty, J. M., Nguyen, T., Heiber, M., Cheng, R., Heng, H. H. Q., Tsui, L.-C., Shi, X., George, S. R., O'Dowd, B. F. Cloning of human genes encoding novel G protein-coupled receptors. Genomics 23: 609-618, 1994. [PubMed: 7851889] [Full Text: https://doi.org/10.1006/geno.1994.1549]
Mehlmann, L. M., Saeki, Y., Tanaka, S., Brennan, T. J., Evsikov, A. V., Pendola, F. L., Knowles, B. B., Eppig, J. J., Jaffe, L. A. The G(S)-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science 306: 1947-1950, 2004. [PubMed: 15591206] [Full Text: https://doi.org/10.1126/science.1103974]
Song, Z.-H., Modi, W., Bonner, T. I. Molecular cloning and chromosomal localization of human genes encoding three closely related G protein-coupled receptors. Genomics 28: 347-349, 1995. [PubMed: 8530049] [Full Text: https://doi.org/10.1006/geno.1995.1154]
Thathiah, A., Spittaels, K., Hoffmann, M., Staes, M., Cohen, A., Horre, K., Vanbrabant, M., Coun, F., Baekelandt, V., Delacourte, A., Fischer, D. F., Pollet, D., De Strooper, B., Merchiers, P. The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science 323: 946-951, 2009. [PubMed: 19213921] [Full Text: https://doi.org/10.1126/science.1160649]