Genomic Analysis of GPR37 and Related Orphan G-Protein Coupled Receptor Genes Highly Expressed in the Mammalian Brain

D.      Marazziti; E.      Golini; A.      Magrelli; R.      Matteoni; G.   P.   Tocchini-Valentini

Abstract

G-protein coupled receptors (GPCRs) constitute the largest set of cell membrane proteins involved in signal transduction and more than half of all drugs currently available influence their activity. Furthermore, genomic sequencing techniques have already enabled the isolation of more than hundred genes that encode so called orphan receptors representing a fruitful resource of potential targets for cellular signaling studies and novel drug discovery. This review focuses on recent progress in molecular cloning, gene organization analysis and chromosomal localization of a new sub-family of mammalian genes encoding the GPR37 (G-Protein coupled orphan Receptor 37) and related proteins. These genes are specifically expressed in brain tissues and they are significantly homologous to endothelin- and bombesin- receptor genes. Comparative genomic analysis has identified two distinct sets of highly conserved human and rodent genes. The first group includes the ortholog genes encoding the putative human, mouse a nd rat GPR37 receptors, also termed ETBR-LP (Endothelin-B Receptor-Like Protein) or GPCR / CNS1 (GPCR / Central Nervous System 1), that are characterised by a relatively large putative extracellular domain (261-249 amino-acids). The second group comprises the genes of the human, mouse and rat GPR37L1 [GPR37-Like protein 1 or ET(B)R-LP-2, GPCR / CNS2] with a shorter (129 amino-acids) extracellular domain. The human and mouse GPR37 and GPR37L1 genes have been shown to contain a single intron interrupting the receptor-coding sequence within the presumed third transmembrane domain. Northern blot analysis and in situ hybridization have shown characteristic patterns of expression of GPR37 and related genes suggesting that they may exert highly specific functions in the mammalian central nervous system.

Keywords: genomic analysis, orphan g-protein coupled, receptor genes, g-protein coupled receptors gpcrs, mammalian gpr genes

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