Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation
Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation
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DOI：
10.1073/pnas.0906695106
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发表时间：
2010-02-02
影响因子：
11.1
通讯作者：
Huhtaniemi, Ilpo
中科院分区：
文献类型：
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作者：
Rivero-Muller, Adolfo;Chou, Yen-Yin;Huhtaniemi, Ilpo
G蛋白偶联受体（GPCR）是激素、神经递质和感觉信号的普遍介质。旧的教条是一个配体/一个受体复合物构成GPCR信号传导的功能单元。然而，越来越多的证据表明，一些GPCR在其生物合成、活化、失活和/或内化过程中形成二聚体或寡聚体。该证据仅从细胞培养实验中获得，并且体内GPCR二聚/寡聚化的生理学意义的证据仍然缺失。使用小鼠促黄体生成激素受体（LHR）作为模型GPCR，我们证明，共表达结合缺陷和信号缺陷形式的LHR的转基因小鼠可以重建正常的LH行动，通过分子间功能互补的突变受体的情况下，功能野生型受体。这些结果提供了令人信服的体内证据的生理相关性的GPCR信号分子间的合作。
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.