G protein-coupled receptor 37 (GPR37) emerges as an important modulator of adenosinergic transmission in the striatum
Xavier Morat
Rodrigo A. Cunha
Francisco Ciruela
摘要：G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G pro-tein-coupled receptor, which suffers a defective parking ubiq-uitination 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 report-ed some functional consequences of this direct interaction, whereby GPR37 deletion enhanced striatal A2AR cell surface expression with a concomitant increase in A2AR agonist-me-diated cAMP accumulation (Morató et al., 2017); accordingly, an enhancement of A2AR agonist-induced catalepsy and antag-onist-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 cur-rent findings now provide additional evidence for the role of GPR37 as a repressor of A2AR function. Thus, while chronic A2AR antagonist treatment (i.e., SCH58261, 1 mg/kg per day, intraperitoneal administration, 10 days) of mice lacking GPR37 did not affect the striatum-dependent cued learning, it en-hanced locomotor sensitization (Morató et al., 2019). Moreover, chronic A2AR blockade boosted striatal long-term depression (LTD) in corticostriatal synapses of GPR37-/- but not of wild type mice; this observation correlated well with the adenosin-ergic neurochemical modifications present in GPR37-/- mice, namely an increased density of A2AR and decreased levels of adenosine (Morató et al., 2019). Overall, GPR37 emerged as key contestant controlling A2AR function particularly upon chronic A2AR blockade, thus delineating A2AR-dependent long-term plastic changes in corticostriatal synapses.
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资助基金：Fondo Europeo de Desarrollo Re-gional (FEDER)/Ministerio de Ciencia)Fondo Europeo de Desarrollo Re-gional ( Innovación y Universi-dades-Agencia Estatal de Investigación(SAF2017-87349-R)Instituto de Salud Carlos III (ISCIII)(PIE14/00034)the Catalan government(2017 SGR 1604)Fundació la Marató de TV3(Grant 20152031)Fonds Wetenschappelijk Onderzoek (FWO) (SBO-140028)Funda??o para a Ciência e a Tecnologia (FCT) (projects PTDC/NEU-NMC/4154/2014 and POCI-01-0145-FEDER-031274)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：3( 1912-1914 )