title: G Protein-Coupled Receptor Heteromers.
abstract: G protein-coupled receptors (GPCRs) compose one of the largest families of membrane proteins involved in intracellular signaling. They are involved in numerous physiological and pathological processes and are prime candidates for drug development. Over the past decade, an increasing number of studies have reported heteromerization between GPCRs. Many investigations in heterologous systems have provided important indications of potential novel pharmacology; however, the physiological relevance of these findings has yet to be established with endogenous receptors in native tissues. In this review, we focus on family A GPCRs and describe the techniques and criteria to assess their heteromerization. We conclude that advances in approaches to study receptor complex functionality in heterologous systems, coupled with techniques that enable specific examination of native receptor heteromers in vivo, are likely to establish GPCR heteromers as novel therapeutic targets.
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029; email: lakshmi.devi@mssm.edu.
authors.forename: Ivone
authors.initials: I
authors.lastname: Gomes
authors.affiliation: Biologie et Bioinformatique des Systèmes de Signalisation (BIOS) Group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements; CNRS, UMR7247, F-37380 Nouzilly, France.|LE STUDIUM Loire Valley Institute for Advanced Studies, F-45000 Orleans, France.
authors.forename: Mohammed Akli
authors.initials: MA
authors.lastname: Ayoub
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029; email: lakshmi.devi@mssm.edu.|Current address: Department of Frontier Life Sciences, Nagasaki University, Nagasaki City, Nagasaki Prefecture 852-8588, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Fujita
authors.affiliation: Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.|Centre for Medical Research, The University of Western Australia, Crawley, Western Australia 6009, Australia.
authors.forename: Werner C
authors.initials: WC
authors.lastname: Jaeger
authors.affiliation: Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia.|Centre for Medical Research, The University of Western Australia, Crawley, Western Australia 6009, Australia.|Dimerix Bioscience Limited, Nedlands, Western Australia 6009, Australia.
authors.forename: Kevin D G
authors.initials: KD
authors.lastname: Pfleger
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029; email: lakshmi.devi@mssm.edu.
authors.forename: Lakshmi A
authors.initials: LA
authors.lastname: Devi
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled
keywords: allosterism; biochemical fingerprint; bivalent ligands; dimerization; heterodimerization; oligomers; proximity-based assays