Rocheville M, Lange D C, Kumar U, Patel S C, Patel R C, Patel Y C
Fraser Laboratories, Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
Science. 2000 Apr 7;288(5463):154-7. doi: 10.1126/science.288.5463.154.
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.
生长抑素和多巴胺是两个主要的神经递质系统，它们具有许多结构和功能特征。生长抑素受体和多巴胺受体在神经元亚群中共定位，并且生长抑素参与调节多巴胺介导的运动活动控制。然而，这两个系统之间这种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SSTR5通过异源寡聚化进行物理相互作用，从而产生一种具有增强功能活性的新型受体。我们的结果提供了证据，表明来自不同G蛋白（异三聚体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。这种直接的膜内缔合定义了相关G蛋白偶联受体亚家族之间分子串扰的一个新水平。
