title: Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation.
abstract: 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.
authors.affiliation: Department of Physiology, University of Turku, 20520 Turku, Finland.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Rivero-Müller
authors.forename: Yen-Yin
authors.initials: YY
authors.lastname: Chou
authors.forename: Inhae
authors.initials: I
authors.lastname: Ji
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lajic
authors.forename: Aylin C
authors.initials: AC
authors.lastname: Hanyaloglu
authors.forename: Kim
authors.initials: K
authors.lastname: Jonas
authors.forename: Nafis
authors.initials: N
authors.lastname: Rahman
authors.forename: Tae H
authors.initials: TH
authors.lastname: Ji
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
mesh_terms: D000818:Animals; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D011974:Receptors, LH / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000378:metabolism / Q000473:pathology
chemical_list: D006063:Chorionic Gonadotropin; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; D011994:Recombinant Proteins