Pharmacological evidence for a metabotropic glutamate receptor heterodimer in neuronal cells
Moreno Delgado, David (Université de Montpellier)
Møller, Thor C. (Université de Montpellier)
Ster, Jeanne (Université de Montpellier)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Laboratori de Neurofarmacologia Molecular i Bioinformàtica)
Maurel, Damien (Université de Montpellier)
Rovira, Xavier (Université de Montpellier)
Scholler, Pauline (Université de Montpellier)
Zwier, Jurriaan M. (CisBio Bioassays, Codolet)
Perroy, Julie (Université de Montpellier)
Durroux, Thierry (Université de Montpellier)
Trinquet, Eric (CisBio Bioassays, Codolet)
Prezeau, Laurent (Université de Montpellier)
Rondard, Philippe (Université de Montpellier)
Pin, Jean-Philippe (Université de Montpellier)

Data:	2017
Resum:	Metabotropic glutamate receptors (mGluRs) are mandatory dimers playing important roles in regulating CNS function. Although assumed to form exclusive homodimers, 16 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.
Ajuts:	Ministerio de Economía y Competitividad PCIN-2013-018-C03-02 Ministerio de Economía y Competitividad SAF2014-58396-R European Commission 627227
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	eLife, Vol. 6 (june 2017) , ISSN 2050-084X

DOI: 10.7554/eLife.25233
PMID: 28661401

33 p, 2.5 MB

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