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Here, we identified GPR37 as an inhibitor of adenosine A<jats:sub>2A<\/jats:sub>receptor (A<jats:sub>2A<\/jats:sub>R) cell surface expression and function<jats:italic>in vivo<\/jats:italic>. In addition, we showed that GPR37 and A<jats:sub>2A<\/jats:sub>R do oligomerize in the striatum. Thus, a close proximity of GPR37 and A<jats:sub>2A<\/jats:sub>R at the postsynaptic level of striatal synapses was observed by double-labelling post-embedding immunogold detection. Indeed, the direct receptor-receptor interaction was further substantiated by proximity ligation<jats:italic>in situ<\/jats:italic>assay. Interestingly, GPR37 deletion promoted striatal A<jats:sub>2A<\/jats:sub>R cell surface expression that correlated well with an increased A<jats:sub>2A<\/jats:sub>R agonist-mediated cAMP accumulation, both in primary striatal neurons and nerve terminals. Furthermore, GPR37\u2212\/\u2212 mice showed enhanced A<jats:sub>2A<\/jats:sub>R agonist-induced catalepsy and an increased response to A<jats:sub>2A<\/jats:sub>R antagonist-mediated locomotor activity. Overall, these results revealed a key role for GPR37 controlling A<jats:sub>2A<\/jats:sub>R biology in the striatum, which may be relevant for PD management.<\/jats:p>","DOI":"10.1038\/s41598-017-10147-x","type":"journal-article","created":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T10:50:17Z","timestamp":1503312617000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The Parkinson\u2019s disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo"],"prefix":"10.1038","volume":"7","author":[{"given":"Xavier","family":"Morat\u00f3","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Luj\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"L\u00f3pez-Cano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gand\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Stagljar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo A.","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Fern\u00e1ndez-Due\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Ciruela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,25]]},"reference":[{"key":"10147_CR1","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/S0169-328X(97)00336-7","volume":"54","author":"PJ Donohue","year":"1998","unstructured":"Donohue, P. 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