GPR37
Description
The GPR37 (G protein-coupled receptor 37) is a protein-coding gene located on chromosome 7.
Probable G-protein coupled receptor 37 is a protein that in humans is encoded by the GPR37 gene. GPR37 is primarily found in the central nervous system (CNS), with significant expression observed in various CNS regions including the amygdala, basal ganglia (caudate, putamen, and nucleus accumbens), substantia nigra, hippocampus, frontal cortex, and hypothalamus, particularly noteworthy is its exceptionally elevated expression in the spinal cord. GPR37 has been shown to interact with HSPA1A and Parkin (ligase). GPR37 is a receptor for prosaposin. It was previously thought to be a receptor for head activator, a neuropeptide found in the hydra, but early reports of head activator in mammals were never confirmed. To address challenges in confirming ligand-GPR37 interactions using recombinant GPR37 expressed in HEK293 cells, recent research has turned to primary cell cultures, leading to successful ligand identification. These investigations have unveiled the involvement of osteocalcin with GPR37 to regulate processes such as oligodendrocyte differentiation, myelination, myelin production, and remyelination following demyelinating injuries. Furthermore, osteocalcin treatment has demonstrated protective effects against Lipopolysaccharide-induced inflammation, which are absent in GPR37-deficient mice. GPR37 signaling has been shown to modulate the migration of olfactory ensheathing cells (OECs) and gonadotropin-releasing hormone (GnRH) cells in mice.
GPR37 is a G-protein-coupled receptor involved in various physiological processes, including the resolution of inflammatory pain and oligodendrocyte differentiation. It acts as a receptor for several ligands, such as prosaposin, osteocalcin, and neuroprotectin D1. Ligand binding initiates endocytosis followed by an ERK phosphorylation cascade. GPR37 functions as a receptor for osteocalcin to regulate oligodendrocyte differentiation and myelination in the central nervous system. It negatively impacts oligodendrocyte differentiation and myelination during development by activating the ERK1/2 signaling pathway, thereby influencing the stability and resistance of myelin to demyelination. Upon activation by neuroprotectin D1, GPR37 promotes phagocytosis in macrophages, shifts cytokine release towards an anti-inflammatory profile, and helps reverse inflammatory pain. Increased macrophage phagocytosis through GPR37 activation provides protection against sepsis during pathogen infection. Extracellular vesicles derived from efferocytes express prosaposin, which binds to macrophage GPR37, leading to increased expression of the efferocytosis receptor TIM4 via an ERK-AP1-dependent signaling axis, accelerating the resolution of inflammation. GPR37 may also serve as a maturation factor for LRP6, shielding it from ER-associated protein degradation and promoting the Wnt/beta-catenin signaling pathway.
GPR37 is also known as EDNRBL, PAELR, hET(B)R-LP.
