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G PROTEIN-COUPLED RECEPTOR 45; GPR45

G PROTEIN-COUPLED RECEPTOR 45; GPR45

HGNC Approved Gene Symbol: GPR45Cytogenetic location: 2q12.1 Genomic coordinates (GRCh38): 2:105,241,742-105,243,466 (from NCBI)▼ DescriptionG protein-couple...

HGNC Approved Gene Symbol: GPR45

Cytogenetic location: 2q12.1 Genomic coordinates (GRCh38): 2:105,241,742-105,243,466 (from NCBI)

▼ Description
G protein-coupled receptors (GPCRs), such as GPR45, are integral membrane proteins containing 7 putative transmembrane domains (TMs). These proteins mediate signals to the interior of the cell via activation of heterotrimeric G proteins that in turn activate various effector proteins, ultimately resulting in a physiologic response (summary by Marchese et al., 1999).

▼ Cloning and Expression
By PCR amplification of human genomic DNA, using degenerate oligonucleotides corresponding to transmembrane domains 3 and 7 of the mouse delta-opioid receptor (165195) and somatostatin receptors (see 182451), Marchese et al. (1999) isolated a cDNA for a novel GPCR that they designated GPR45. The 11-kb GPR45 gene encodes a 372-amino acid protein that shows 70% amino acid sequence identity to the Xenopus oocyte receptor PSP24, a putative lysophosphatidic acid receptor. Northern blot analysis detected a 4.25-kb transcript in basal forebrain, frontal cortex, and caudate, but not in thalamus, hippocampus, or putamen. A 3.0-kb transcript was detected in liver.

Using RT-PCR, Cui et al. (2016) found that Gpr45 was expressed in several regions of mouse brain and in testis, but not in other mouse tissues examined. Highest expression was in hypothalamus.

▼ Mapping
By fluorescence in situ hybridization, Marchese et al. (1999) mapped the GPR45 gene to chromosome 2q11.2-q12.

Hartz (2017) mapped the GPR45 gene to chromosome 2q12.1 based on an alignment of the GPR45 sequence (GenBank U92642) with the genomic sequence (GRCh38).

▼ Animal Model
Using insertional mutagenesis, Cui et al. (2016) generated a mouse line with disrupted Gpr45 expression due to an insertion upstream of the Gpr45 coding exon. Gpr45 mutants became obese after weaning, but they did not show changes in food intake. Prior to onset of obesity, mutant mice exhibited reduced physical activity and energy expenditure. Adult Gpr45 mutants displayed elevated fat content, glucose intolerance, insulin (INS; 176730) resistance, and hepatic steatosis with advancing age. Metabolically, Gpr45 mutant mice showed elevated fasting plasma leptin (LEP; 164160) and insulin levels and reduced expression of the metabolic regulator Pomc (176830). Administration of an analog of a Pomc-derived hormone suppressed adult obesity in Gpr45 mutants. In culture, primary Gpr45 mutant embryonic hypothalamic cells showed reduced Pomc expression, membrane hyperpolarization, and reduced Jak2 (147796) and Stat3 (102582) phosphorylation. Immunoprecipitation and pull-down experiments showed that Gpr45 interacted directly with Jak2. Chromatin immunoprecipitation analysis revealed reduced recruitment of Stat3 to the Pomc promoter in Gpr45 mutant hypothalamus. Cui et al. (2016) concluded that GPR45 influences body mass by regulating POMC signaling via the JAK/STAT pathway.

Tags: 2q12.1