Rescue of defective G protein–coupled receptor function in vivo by intermolecular cooperation

• DOI: 10.1073/pnas.0906695106
• Publication Date: 2010-01-12T03:29:07Z
• Authors: Adolfo Rivero-Müller; Yen-Yin Chou; Inhae Ji; Svetlana Lajic; Aylin C. Hanyaloglu; Kim Jonas; Nafis Rahman; Tae H. Ji; Ilpo Huhtaniemi
• Keywords: Internalization; Bimolecular fluorescence complementation; Cell Signaling; Rhodopsin-like receptors

G protein–coupled receptors (GPCRs) are ubiquitous mediators of signaling hormones, neurotransmitters, and sensing. The old dogma is that a one ligand/one receptor complex constitutes the functional unit GPCR signaling. However, there mounting evidence some GPCRs form dimers or oligomers during their biosynthesis, activation, inactivation, and/or internalization. This has been obtained exclusively from cell culture experiments, proof for physiological significance di/oligomerization in vivo still missing. Using mouse luteinizing hormone (LHR) as model GPCR, we demonstrate transgenic mice coexpressing binding-deficient signaling-deficient forms LHR can reestablish normal LH actions through intermolecular complementation mutant absence wild-type receptors. These results provide compelling relevance cooperation