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Title:	The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo
Author:	Morató Arús, Xavier; Luján, Rafael; López-Cano, Marc; Gandía Sánchez, Jorge; Stagljar, Igor; Watanabe, Masahiko; Cunha, Rodrigo A.; Fernández Dueñas, Víctor; Ciruela Alférez, Francisco
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.
Subject(s):	-Malaltia de Parkinson -Proteïnes G -Adenosina -Marcadors bioquímics -Receptors de neurotransmissors -Parkinson's disease -G Proteins -Adenosine -Biochemical markers -Neurotransmitter receptors
Rights:	cc-by (c) Morató Arús, Xavier et al., 2017 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Nature Publishing Group
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