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The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo.


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.

SUBMITTER: Morato X 

PROVIDER: S-EPMC5573386 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A<sub>2A</sub> receptor controlling its cell surface expression and function in vivo.

Morató Xavier X   Luján Rafael R   López-Cano Marc M   Gandía Jorge J   Stagljar Igor I   Watanabe Masahiko M   Cunha Rodrigo A RA   Fernández-Dueñas Víctor V   Ciruela Francisco F  

Scientific reports 20170825 1


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 A<sub>2A</sub> receptor (A<sub>2A</sub>R) cell surface expression and function in vivo. In addition, we showed that GPR37 and A<sub>2A</sub>R do oligomerize in the striatum. Thus, a close proximity of GPR37 and A<sub>2A</sub>R at the postsynaptic level of striatal synapses was observed by double-labelling post-embedding immunogo  ...[more]

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