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PMID: 20080658 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 5 ·2010-02-02 ·Pages 2319-24

Rivero-Müller A, Chou YY, Ji I, Lajic S, Hanyaloglu AC, Jonas K, Rahman N, Ji TH, Huhtaniemi I

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.

MeSH Terms
Animals Cell Line Chorionic Gonadotropin/metabolism Genetic Complementation Test Humans Male Mice Mice, Knockout Mice, Mutant Strains Mice, Transgenic Models, Biological Models, Molecular Mutation Phenotype Protein Binding Protein Multimerization Receptors, G-Protein-Coupled/chemistry,metabolism Receptors, LH/chemistry,deficiency,genetics,metabolism Recombinant Proteins/chemistry,genetics,metabolism Signal Transduction Testis/metabolism,pathology
Chemicals
Chorionic Gonadotropin Receptors, G-Protein-Coupled Receptors, LH Recombinant Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rivero-Müller Adolfo
Department of Physiology, University of Turku, 20520 Turku, Finland.
Chou Yen-Yin
Ji Inhae
Lajic Svetlana
Hanyaloglu Aylin C
Jonas Kim
Rahman Nafis
Ji Tae H
Huhtaniemi Ilpo
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0906695106
Published
2010-02-02
Epub
2010-00-11
Pages
2319-24
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2836644
Subset
IM
Grants
Wellcome Trust · United Kingdom
Corrections
CommentIn
PMID: 20133832
External Links
PubMed source DOI: 10.1073/pnas.0906695106 PMC Full Text View journal details
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