Pharmacological evidence for a metabotropic glutamate receptor heterodimer in neuronal cells
- CNRS, INSERM, Univ Montpellier, France
- CNRS, INSERM, Université de Montpellier, France
- Universitat Autònoma de Barcelona, Spain
- Cisbio bioassays, France
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.
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Author details
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.
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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Pharmacological evidence for a metabotropic glutamate receptor heterodimer in neuronal cells
eLife 6:e25233.
https://doi.org/10.7554/eLife.25233
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