Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/108379
Title: The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo
Authors: Morató, Xavier
Luján, Rafael
López-Cano, Marc
Gandía, Jorge
Stagljar, Igor
Watanabe, Masahiko
Cunha, Rodrigo A. 
Fernández-Dueñas, Víctor
Ciruela, Francisco 
Issue Date: 25-Aug-2017
Publisher: Springer Nature
Project: MINECO/ISCIII (SAF2014–55700-P and PIE14/00034) 
Catalan government (2014 SGR 1054) 
Fundació la Marató de TV3 (Grant 20152031) and FWO (SBO-140028) 
Santa Casa da Misericórdia 
MINECO (BFU-2015-63769-R) 
Junta de Comunidades de Castilla-La Mancha (PPII-2014-005-P) 
European Union (HBP - Project Ref. 604102) 
Serial title, monograph or event: Scientific Reports
Volume: 7
Issue: 1
Abstract: G protein-coupled receptor 37 (GPR37) is an orphan receptor associated to Parkinson's disease (PD) neuropathology. Here, we identified GPR37 as an inhibitor of adenosine A2A receptor (A2AR) cell surface expression and function in vivo. In addition, we showed that GPR37 and A2AR do oligomerize in the striatum. Thus, a close proximity of GPR37 and A2AR 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 in situ assay. Interestingly, GPR37 deletion promoted striatal A2AR cell surface expression that correlated well with an increased A2AR agonist-mediated cAMP accumulation, both in primary striatal neurons and nerve terminals. Furthermore, GPR37-/- mice showed enhanced A2AR agonist-induced catalepsy and an increased response to A2AR antagonist-mediated locomotor activity. Overall, these results revealed a key role for GPR37 controlling A2AR biology in the striatum, which may be relevant for PD management.
URI: https://hdl.handle.net/10316/108379
ISSN: 2045-2322
DOI: 10.1038/s41598-017-10147-x
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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