The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A(2A) receptor controlling its cell surface expression and function in vivo.
The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A(2A) receptor controlling its cell surface expression and function in vivo.
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帕金森氏病相关的GPR37受体与纹状体腺苷A（2a）受体相互作用，该受体控制其细胞表面表达和体内功能。
DOI：
10.1038/s41598-017-10147-x
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发表时间：
2017-08-25
影响因子：
4.6
通讯作者：
Ciruela F
中科院分区：
文献类型：
--
作者：
Morató X;Luján R;López-Cano M;Gandía J;Stagljar I;Watanabe M;Cunha RA;Fernández-Dueñas V;Ciruela F
G蛋白偶联受体37（GPR 37）是一种与帕金森病（PD）神经病理学相关的孤儿受体。在这里，我们确定GPR 37作为腺苷A2 A受体（A2 AR）细胞表面表达和功能的抑制剂在体内。此外，我们发现GPR 37和A2 AR在纹状体中确实寡聚化。因此，紧密接近的GPR 37和A2 AR在突触后水平的纹状体突触观察到双标记后嵌入免疫金检测。事实上，直接受体-受体相互作用进一步证实了邻近连接原位测定。有趣的是，GPR 37缺失促进了纹状体A2 AR细胞表面表达，这与A2 AR激动剂介导的cAMP积累增加密切相关，无论是在初级纹状体神经元还是神经末梢中。此外，GPR 37 −/−小鼠表现出增强的A2 AR激动剂诱导的僵住症和对A2 AR拮抗剂介导的运动活性的反应增加。总体而言，这些结果揭示了GPR 37在纹状体中控制A2 AR生物学的关键作用，这可能与PD管理相关。
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.
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影响因子：
4.7
作者：
Khisti, RT;Chopde, CT;Abraham, E
通讯作者：
Abraham, E
影响因子：
3.5
作者：
Kitao, Yasuko;Imai, Yuzuru;Ogawa, Satoshi
通讯作者：
Ogawa, Satoshi
影响因子：
4
作者：
Fernandez-Duenas, Victor;Gomez-Soler, Maricel;Lopez-Cano, Marc;Taura, Jaume J.;Ledent, Catherine;Watanabe, Masahiko;Jacobson, Kenneth A.;Vilardaga, Jean-Pierre;Ciruela, Francisco
通讯作者：
Ciruela, Francisco
影响因子：
2.9
作者：
Imai, Yuzuru;Inoue, Haruhisa;Takahashi, Ryosuke
通讯作者：
Takahashi, Ryosuke
DOI：
10.1073/pnas.0703368104
发表时间：
2007-06-05
影响因子：
11.1
作者：
Marazziti, Daniela;Mandillo, Silvia;Tocchini-Valentini, Glauco P.
通讯作者：
Tocchini-Valentini, Glauco P.