Abstract
Chemerin, a chemoattractant protein and adipokine, has been identified as the endogenous ligand for a G protein–coupled receptor encoded by the gene CMKLR1 (also known as ChemR23), and as a consequence the receptor protein was renamed the chemerin receptor in 2013. Since then, chemerin has been identified as the endogenous ligand for a second G protein–coupled receptor, encoded by the gene GPR1. Therefore, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification recommends that the official name of the receptor protein for chemokine-like receptor 1 (CMKLR1) is chemerin receptor 1, and G protein–coupled receptor 1 is chemerin receptor 2 to follow the convention of naming the receptor protein after the endogenous ligand. Chemerin receptor 1 and chemerin receptor 2 can be abbreviated to Chemerin1 and Chemerin2, respectively. Chemerin requires C-terminal processing for activity, and human chemerin21–157 is reported to be the most active form, with peptide fragments derived from the C terminus biologically active at both receptors. Small-molecule antagonist, CCX832, selectively blocks CMKLR1, and resolvin E1 activation of CMKLR1 is discussed. Activation of both receptors by chemerin is via coupling to Gi/o, causing inhibition of adenylyl cyclase and increased Ca2+ flux. Receptors and ligand are widely expressed in humans, rats, and mice, and both receptors share ∼80% identity across these species. CMKLR1 knockout mice highlight the role of this receptor in inflammation and obesity, and similarly, GPR1 knockout mice exhibit glucose intolerance. In addition, the chemerin receptors have been implicated in cardiovascular disease, cancer, steroidogenesis, human immunodeficiency virus replication, and neurogenerative disease.
Highlights
Chemerin, the endogenous ligand of chemokine-like receptor 1 (CMKLR1) or ChemR23, was identified in 2003 as the product of the retinoic acid receptor responder 2 protein (RARRES2) gene (Meder et al, 2003; Wittamer et al, 2003)
Abstract——Chemerin, a chemoattractant protein and adipokine, has been identified as the endogenous ligand for a G protein–coupled receptor encoded by the gene CMKLR1, and as a consequence the receptor protein was renamed the chemerin receptor in 2013
The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification recommends that the official name of the receptor protein for chemokine-like receptor 1 (CMKLR1) is chemerin receptor 1, and G protein–coupled receptor 1 is chemerin receptor 2 to follow the convention of naming the receptor protein after the endogenous ligand
Summary
The endogenous ligand of chemokine-like receptor 1 (CMKLR1) or ChemR23, was identified in 2003 as the product of the RARRES2 gene (Meder et al, 2003; Wittamer et al, 2003). The C terminus is very important for function at CMKLR1, exemplified further by synthetic C-terminal fragments of human chemerin: C9 (or chemerin-9), chemerin149157; C13, chemerin145157 (Wittamer et al, 2004); and C20, chemerin138157 (Li et al, 2014a), possessing biologic activity (Fig. 1C). It is not yet known whether these short peptides are generated endogenously. Names of genes should be italicized and, consistent with the Human Genome Organization, CMKLR1 refers to chemerin receptor 1, GPR1 refers to chemerin receptor 2, and RARRES2 refers to chemerin, with lower case letters used for nonhuman species (Table 2)
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