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Review ArticleReview Article

G Protein–Coupled Receptor Oligomerization Revisited: Functional and Pharmacological Perspectives

Sergi Ferré, Vicent Casadó, Lakshmi A. Devi, Marta Filizola, Ralf Jockers, Martin J. Lohse, Graeme Milligan, Jean-Philippe Pin and Xavier Guitart
Mark P. Mattson, ASSOCIATE EDITOR
Pharmacological Reviews April 2014, 66 (2) 413-434; DOI: https://doi.org/10.1124/pr.113.008052
Sergi Ferré
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Vicent Casadó
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Lakshmi A. Devi
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Marta Filizola
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Ralf Jockers
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Martin J. Lohse
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Graeme Milligan
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Jean-Philippe Pin
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Xavier Guitart
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
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Mark P. Mattson
Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
Roles: ASSOCIATE EDITOR
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Article Information

vol. 66 no. 2 413-434
DOI 
https://doi.org/10.1124/pr.113.008052
PubMed 
24515647

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0031-6997
Online ISSN 
1521-0081
History 
  • Published online February 10, 2014.

Copyright & Usage 
U.S. Government work not protected by U.S. copyright

Author Information

  1. Sergi Ferré,
  2. Vicent Casadó,
  3. Lakshmi A. Devi,
  4. Marta Filizola,
  5. Ralf Jockers,
  6. Martin J. Lohse,
  7. Graeme Milligan,
  8. Jean-Philippe Pin, and
  9. Xavier Guitart
  1. Integrative Neurobiology Section, National Institute on Drug Addiction, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland (S.F., X.G.); Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain (V.C.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain (V.C.); Department of Pharmacology and Systems Therapeutics (L.A.D.) and Department of Structural and Chemical Biology (M.F.), Icahn School of Medicine at Mount Sinai, Mount Sinai, New York; Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France (R.J.); Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris, France (R.J.); Universite Paris Descartes, Sorbone Paris Cite, Paris, France (R.J.); Institute of Pharmacology and Toxicology and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom (G.M.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Université Montpellier, Montpellier, France (J.-P.P.); and Institut National de la Santé et de la Recherche Médicale, U661, Montpellier, France (J.-P.P.)
  1. Mark P. Mattson, ASSOCIATE EDITOR
  1. Address correspondence to:
    Sergi Ferré, Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes on Drug Abuse, Department of Health and Human Services, 333 Cassell Drive, Baltimore, Maryland 21224. E-mail: sferre{at}intra.nida.nih.gov
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Pharmacological Reviews: 66 (2)
Pharmacological Reviews
Vol. 66, Issue 2
1 Apr 2014
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Review ArticleReview Article

G Protein–Coupled Receptor Oligomerization

Sergi Ferré, Vicent Casadó, Lakshmi A. Devi, Marta Filizola, Ralf Jockers, Martin J. Lohse, Graeme Milligan, Jean-Philippe Pin and Xavier Guitart
Pharmacological Reviews April 1, 2014, 66 (2) 413-434; DOI: https://doi.org/10.1124/pr.113.008052

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Review ArticleReview Article

G Protein–Coupled Receptor Oligomerization

Sergi Ferré, Vicent Casadó, Lakshmi A. Devi, Marta Filizola, Ralf Jockers, Martin J. Lohse, Graeme Milligan, Jean-Philippe Pin and Xavier Guitart
Pharmacological Reviews April 1, 2014, 66 (2) 413-434; DOI: https://doi.org/10.1124/pr.113.008052
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  • Article
    • Abstract
    • I. Morphologic Aspects of G Protein–Coupled Receptor Oligomerization
    • II. Functional Aspects of G Protein–Coupled Receptor Oligomerization
    • III. G Protein–Coupled Receptor Oligomers as Novel Targets for Drug Development
    • Acknowledgments
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