G protein-coupled receptor 37 (GPR37) emerges as an important modulator of adenosinergic transmission in the striatum

Abstract

G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein-coupled receptor, which suffers a defective parking ubiquitination in autosomal recessive Parkinson's disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death (Takahashi and Imai, 2003). Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A2A receptor (A2AR) in the striatum (Morató et al., 2017; Sokolina et al., 2017). In addition, we also reported some functional consequences of this direct interaction, whereby GPR37 deletion enhanced striatal A2AR cell surface expression with a concomitant increase in A2AR agonist-mediated cAMP accumulation (Morató et al., 2017); accordingly, an enhancement of A2AR agonist-induced catalepsy and antagonist-induced locomotor activity was observed upon GPR37 deletion (Morató et al., 2017). Overall, it has been hypothesized that GPR37 might hold a chaperone-like activity controlling A2AR cell surface targeting and function. However, the precise physiological function of GPR37 still is unidentified. The current findings now provide additional evidence for the role of GPR37 as a repressor of A2AR function.