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

Adolfo Rivero-Müller, Yen Yin Chou, Inhae Ji, Svetlana Lajic, Aylin C. Hanyaloglu, Kim Jonas, Nafis Rahman, Tae H. Ji, Ilpo Huhtaniemi

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2319-2324
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number5
DOIs
Publication statusPublished - 2010 Feb 2

All Science Journal Classification (ASJC) codes

  • General

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