INSERM UMR-S839, S1270, Paris, 75005, France; Sorbonne Université, Paris, 75005, France; Institut du Fer à Moulin, Paris, 75005, France.
INSERM UMR-S839, S1270, Paris, 75005, France; Sorbonne Université, Paris, 75005, France; Institut du Fer à Moulin, Paris, 75005, France.
Biochimie. 2019 Jun;161:23-33. doi: 10.1016/j.biochi.2019.01.009. Epub 2019 Jan 24.
Membrane receptors often form complexes with other membrane proteins that directly interact with different effectors of the signal transduction machinery. G-protein-coupled receptors (GPCRs) were for long time considered as single pharmacological entities. However, evidence for oligomerization appeared for various classes and subtypes of GPCRs. This review focuses on metabotropic serotonin (5-hydroxytryptamine, 5-HT) receptors, which belong to the rhodopsin-like class A of GPCRs, and will summarize the convergent evidence that homo- and hetero-dimers containing 5-HT receptors exist in transfected cells and in-vivo. We will show that complexes involving 5-HT receptors may acquire new signal transduction pathways and new physiological roles. In some cases, these complexes participate in disease-specific deregulations, that can be differentially affected by various drugs. Hence, selecting receptor complex-specific responses of these heterodimers may constitute an emerging strategy likely to improve beneficial therapeutic effects.
膜受体通常与其他膜蛋白形成复合物，这些复合物直接与信号转导机制的不同效应器相互作用。G 蛋白偶联受体（GPCR）长期以来被认为是单一的药理学实体。然而，各种 GPCR 类和亚型的寡聚化证据已经出现。这篇综述重点介绍代谢型血清素（5-羟色胺，5-HT）受体，它属于 GPCR 的视紫红质样 A 类，并将总结包含 5-HT 受体的同源和异源二聚体存在于转染细胞和体内的汇聚证据。我们将表明，涉及 5-HT 受体的复合物可能获得新的信号转导途径和新的生理作用。在某些情况下，这些复合物参与特定疾病的失调，这些失调可能会受到各种药物的不同影响。因此，选择这些异源二聚体的受体复合物特异性反应可能构成一种新兴的策略，有望提高有益的治疗效果。
