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Pharmacological evidence for a metabotropic glutamate receptor heterodimer in neuronal cells

  1. David Moreno Delgado
  2. Thor C Møller
  3. Jeanne Ster
  4. Jesús Giraldo
  5. Damien Maurel
  6. Xavier Rovira
  7. Pauline Scholler
  8. Jurrian M Zwier
  9. Julie Perroy
  10. Thierry Durroux
  11. Eric Trinquet
  12. Laurent Prezeau
  13. Philippe Rondard
  14. Jean-Philippe Pin  Is a corresponding author
  1. CNRS, INSERM, Univ Montpellier, France
  2. CNRS, INSERM, Université de Montpellier, France
  3. Universitat Autònoma de Barcelona, Spain
  4. Cisbio bioassays, France
Research Article
  • Cited 18
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Cite this article as: eLife 2017;6:e25233 doi: 10.7554/eLife.25233

Abstract

Metabotropic glutamate receptors (mGluRs) are mandatory dimers playing important roles in regulating CNS function. Although assumed to form exclusive homodimers, sixteen possible heterodimeric mGluRs have been proposed but their existence in native cells remains elusive. Here we set up two assays to specifically identify the pharmacological properties of rat mGlu heterodimers composed of mGlu2 and 4 subunits. We used either a heterodimer specific conformational LRET-based biosensor, or a system that guarantees the cell surface targeting of the heterodimer only. We identified mGlu2-4 specific pharmacological fingerprints that were also observed in a neuronal cell line and in lateral perforant path terminals naturally expressing mGlu2 and mGlu4. These results bring strong evidence for the existence of mGlu2-4 heterodimers in native cells. In addition to reporting a general approach to characterize heterodimeric mGluRs, our study opens new avenues to understanding the pathophysiological roles of mGlu heterodimers.

Article and author information

Author details

  1. David Moreno Delgado

    Institut de Genomique Fonctionnelle, CNRS, INSERM, Univ Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  2. Thor C Møller

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  3. Jeanne Ster

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  4. Jesús Giraldo

    Laboratory of Molecular Neuropharmacology and Bioinformatics, Universitat Autònoma de Barcelona, Bellaterra, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7082-4695
  5. Damien Maurel

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  6. Xavier Rovira

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9764-9927
  7. Pauline Scholler

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  8. Jurrian M Zwier

    Cisbio bioassays, Codolet, France
    Competing interests
    Jurrian M Zwier, Dr Zwier is working at Cisbio Bioassays, a company selling HTRF tools.
  9. Julie Perroy

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  10. Thierry Durroux

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  11. Eric Trinquet

    Cisbio bioassays, Codolet, France
    Competing interests
    Eric Trinquet, He is head of R&D at CisBio Bioassays.
  12. Laurent Prezeau

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  13. Philippe Rondard

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  14. Jean-Philippe Pin

    Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
    For correspondence
    jppin@igf.cnrs.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1423-345X

Funding

Fondation recherche médicale DEQ20130326522 (DEQ20130326522)

  • Jean-Philippe Pin

CisBio bioassays (Laboratoire Collaboratif)

  • Jean-Philippe Pin

ERA-NET Neuron (PCIN-2013-018-C03-02)

  • Jesús Giraldo

ERA-NET Neuron (SAF2014-58396-R)

  • Jesús Giraldo

Agence Nationale de la Recherche (ANR-09-BIOT-018)

  • Eric Trinquet
  • Philippe Rondard
  • Jean-Philippe Pin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Publication history

  1. Received: January 18, 2017
  2. Accepted: June 26, 2017
  3. Accepted Manuscript published: June 29, 2017 (version 1)
  4. Version of Record published: August 2, 2017 (version 2)

Copyright

© 2017, Moreno Delgado et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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