Department of Physiology, University of Turku, 20520 Turku, Finland.
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24. doi: 10.1073/pnas.0906695106. Epub 2010 Jan 11.
G protein-coupled receptors (GPCRs) are ubiquitous mediators of signaling of hormones, neurotransmitters, and sensing. The old dogma is that a one ligand/one receptor complex constitutes the functional unit of GPCR signaling. However, there is mounting evidence that some GPCRs form dimers or oligomers during their biosynthesis, activation, inactivation, and/or internalization. This evidence has been obtained exclusively from cell culture experiments, and proof for the physiological significance of GPCR di/oligomerization in vivo is still missing. Using the mouse luteinizing hormone receptor (LHR) as a model GPCR, we demonstrate that transgenic mice coexpressing binding-deficient and signaling-deficient forms of LHR can reestablish normal LH actions through intermolecular functional complementation of the mutant receptors in the absence of functional wild-type receptors. These results provide compelling in vivo evidence for the physiological relevance of intermolecular cooperation in GPCR signaling.
G 蛋白偶联受体（GPCRs）是激素、神经递质和感应的信号转导的普遍介质。旧的教条认为，一个配体/一个受体复合物构成了 GPCR 信号转导的功能单位。然而，越来越多的证据表明，一些 GPCRs 在其生物合成、激活、失活和/或内化过程中形成二聚体或寡聚体。这些证据仅来自细胞培养实验，体内 GPCR 二聚化/寡聚化的生理意义的证据仍然缺失。我们使用小鼠促黄体激素受体（LHR）作为模型 GPCR，证明共表达结合缺陷和信号缺陷形式的 LHR 的转基因小鼠可以通过突变受体在没有功能型野生型受体的情况下的分子间功能互补，重新建立正常的 LH 作用。这些结果为 GPCR 信号转导中分子间合作的生理相关性提供了令人信服的体内证据。
