Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation.
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.
Rivero-Müller
Adolfo
A
Department of Physiology, University of Turku, 20520 Turku, Finland.
Chou
Yen-Yin
YY
Ji
Inhae
I
Lajic
Svetlana
S
Hanyaloglu
Aylin C
AC
Jonas
Kim
K
Rahman
Nafis
N
Ji
Tae H
TH
Huhtaniemi
Ilpo
I
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
D006063:Chorionic Gonadotropin; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; D011994:Recombinant Proteins