Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
FEBS Lett. 2021 Jul;595(14):1863-1875. doi: 10.1002/1873-3468.14135. Epub 2021 Jun 11.
Although class A seven-transmembrane helix (7TM) receptor hetero-oligomers have been proposed, information on the assembly and function of such higher-order hetero-oligomers is not available. Utilizing bioluminescence resonance energy transfer (BRET), bimolecular luminescence/fluorescence complementation (BiLC/BiFC), and BiLC/BiFC BRET in HEK293T cells, we provide evidence that chemokine (C-X-C motif) receptor 4, atypical chemokine receptor 3, α -adrenoceptor, and arginine vasopressin receptor 1A form hetero-oligomers composed of 2-4 different protomers. We show that hetero-oligomerization per se and ligand binding to individual protomers regulate agonist-induced coupling to the signaling transducers of interacting receptor partners. Our findings support the concept that receptor hetero-oligomers form supramolecular machineries with molecular signaling properties distinct from the individual protomers. These findings provide a mechanism for the phenomenon of context-dependent receptor function.
虽然已经提出了 A 类七跨膜螺旋 (7TM) 受体异源寡聚体，但关于这种更高阶异源寡聚体的组装和功能的信息尚不清楚。利用生物发光共振能量转移 (BRET)、双分子发光/荧光互补 (BiLC/BiFC) 和 BiLC/BiFC BRET，我们在 HEK293T 细胞中提供了证据，表明趋化因子 (C-X-C 基序) 受体 4、非典型趋化因子受体 3、α-肾上腺素受体和精氨酸加压素受体 1A 形成由 2-4 种不同的原聚体组成的异源寡聚体。我们表明，异源寡聚化本身以及配体与单个原聚体的结合调节与相互作用的受体伙伴的信号转导物的激动剂诱导偶联。我们的发现支持这样一种概念，即受体异源寡聚体形成具有与单个原聚体不同的分子信号特性的超分子机器。这些发现为受体功能的上下文依赖性现象提供了一种机制。
