Receptors for dopamine and somatostatin: Formation of hetero-oligomers with enhanced functional activity

Receptors for dopamine and somatostatin: Formation of hetero-oligomers with enhanced functional activity
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DOI:
10.1126/science.288.5463.154
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发表时间:
2000-04-07
期刊:
影响因子:
56.9
通讯作者:
Patel, YC
Patel, YC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Rocheville, M;Lange, DC;Patel, YC

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生长抑素和多巴胺是两种主要的神经递质系统,它们具有许多共同的结构和功能特征。生长抑素受体和多巴胺受体共定位于神经元亚群中,并且生长抑素参与调节多巴胺介导的运动活动控制。然而,这两个系统之间的相互作用的分子基础尚不清楚。在这里,我们表明,多巴胺受体D2R和生长抑素受体SSTR 5通过异源寡聚化物理相互作用,以创建一个新的受体,增强功能活性。我们的研究结果提供了证据,从不同的G蛋白(异源三聚鸟嘌呤核苷酸结合蛋白)偶联受体家族的受体通过寡聚化相互作用。这种直接的膜内关联定义了相关G蛋白偶联受体亚家族之间的分子串扰的新水平。
Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.