A new family of orphan G protein‐coupled receptors predominantly expressed in the brain¹

Abstract

The cloning of a cDNA encoding a G protein-coupled receptor homologous to the endothelin type B receptor, but unable to bind endothelin, was recently reported and termed ET f R-LP. We report here the isolation of a human cDNA encoding a receptor that is highly related to ET f R-LP and which was therefore termed ET f R-LP-2. Comparison of the two amino acid sequences revealed 68% overall homology and 48% identity. As is the case for ET f R-LP, the new receptor is strongly expressed in the human central nervous system (e.g. in cerebellar Bergmann glia, cerebral cortex, internal capsule fibers). Membranes of HEK-293 cells stably expressing ET f R-LP-2 did not bind endothelin-1, endothelin-2, endothelin-3, bombesin, cholecystokinin-8 or gastrin-releasing peptide.z 1998 Federation of European Biochemical Societies.

Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor

“…1A), consistent with the expression pattern of the Gpr37l1 gene by in situ hybridization (ISH) in whole brain sections of newborn and adult C57BL/6J mice ( Fig. S1 A and B) (17). The receptor protein was found colocalized with the astrocytic glial high-affinity glutamate transporter (Glast), with typical staining of reticular and fibrous structures, in the ML and EGL, respectively ( Fig.…”

“…The reported immunolabeling analysis reveals that the Gpr37l1 protein is specifically and progressively expressed in cell bodies and fibrous processes of cerebellar Bergmann glia from the earliest neonatal phases to the adult stage ( Fig. 1 A and B), whereas it is not expressed in newborn and adult cerebellar granule and Purkinje neuronal cells, as reported (15,17,28). Thus, Gpr37l1 is a specific marker of murine Bergmann astrocytes.…”

“…Among them, the GPR37L1 gene was found highly expressed in developing (Cerebellar Development Transcriptome Database, accession no. CD06446) and adult Bergmann glia astrocytes (17). It was also identified as a modulator of the genesis and assembly of the primary cilium, a cellular organelle required for Shh-Smo signaling (18,19).…”

“…5439168 (Gpr37l1<tm1.1Gtva>) and 5439169 (Gpr37l1<tm1.2Gtva>)]. G-protein-coupled receptors for the endothelin and bombesin peptides (17,20,21). Recently, the secreted neuro-and glioprotective glycoprotein prosaposin and derived peptides have been shown in vitro to interact with and activate both putative receptors (22).…”

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

“…In contrast to the mixed distribution of GPR37, GPR37L1 is highly expressed in astrocytes, with in situ hybridization revealing greatest density of GPR37L1 within the Bergmann glia of the cerebellum (Valdenaire et al, 1998). Microarray studies reported more than 100 times higher expression of GPR37L1 in rat and mice astrocytes compared with neurons (Cahoy et al, 2008; Lovatt et al, 2007; Zhang et al, 2014).…”