NEURORECEPTORS, DYNAMICS AND FUNCTION
Department: Neurosciences - Research axis: GPCR signaling

Research subject

Glutamate and gamma-amminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters of the nervous system. They act on ligand-gated ion channels which are responsible for fast synaptic responses. They also modulate synaptic activity through the activation of G protein-coupled receptors (GPCR): metabotropic glutamate receptors (mGlu) and GABAB receptors. These receptors are considered as promising therapeutic targets for the treatment of various neurological and psychiatric disorders.

To identify new means and strategies to modulate their activity in vivo, our team is working at deciphering their mechanisms of activation at molecular and cellular levels, and at analyzing their association in signaling protein complexes. Thanks to the development of new technologies, we have revealed novel concepts about GPCR function, notably their association in dimers and higher order oligomers, and their asymmetrical mode of action. This knowledge allows us to identify new agents acting on mGlu and GABAB receptors and to highlight their therapeutic potential in Parkinson’s disease and pain.

Team Supported by the Fondation pour la Recherche Médicale (FRM DEQ20130326522)

 

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Team

Team leader

Jean-Philippe Pin
DRCE, CNRS


  IGF Nord 223b

  04 34 35 92 89

 

Laurent Prezeau
DR2, CNRS


  IGF Nord 221a

  04 34 35 92 96

 

Staff

Isabelle Brabet
IECN, CNRS


  IGF Nord 219

  04 34 35 93 13

 

Léa Clusan
IE CDD, CNRS


  IGF Nord 221

  04 34 35 93 07

 

Cécile Derieux
Stagiaire, CNRS


  IGF Nord 212b

  04 34 35 93 30

 

Joan Font-Ingles
Post-doctorant(e), CNRS


  IGF Nord 221a

  04 34 35 93 07

 

Cyril Goudet
CRCN, CNRS


  IGF Nord 209a

  04 34 35 92 77

 

Flavien Grégoire
IE CDD, CNRS


  IGF Nord 221a

  04 34 35 93 07

 

Jordi Haubrich
Doctorant(e), Inserm


  IGF Nord 215

  04 34 35 92 78

 

Julie Kniazeff
CRCN, CNRS


  IGF Nord 221a

  04 34 35 92 96

 

Fanny Malhaire
IE CDI, CNRS


  IGF Nord 209a

  04 34 35 92 77

 

Michaël Mathieu
IE CDD, CNRS


  IGF Nord 215a

  04 34 35 92 78

 

JiYong Meng
Doctorant(e), CNRS


  IGF Nord 215a

  04 34 35 92 78

 

Mathieu Oosterlaken
Doctorant(e), UM


  IGF Nord 221a

  04 34 35 93 07

 

Marine Papin
Master 2, CNRS


  IGF Nord 221

  04 34 35 92 96

 

Vanessa Pereira
Post-doctorant(e), CNRS


  IGF Nord 209a

  04 34 35 92 77

 

Maria Ricart-Ortega
Accueil scientifique, CNRS


  IGf Nord 205

  04 34 35 92 77

 

Lois Rodriguez
Master 2, CNRS


  IGF Nord 221

  04 34 35 92 96

 

Philippe Rondard
DR2, Inserm


  IGF Nord 215b

  04 34 35 92 78

 

Cédric Soulie
Master 1, CNRS


  IGF Nord 215a

  04 34 35 92 78

 

Julien Soulé
IECN, CNRS


  IGF Nord 215a

  04 34 35 92 78

 

Scherrine Tria
IR CDD, CNRS


  IGF Nord 215b

  04 34 35 92 78

 

Claire Vol
IECN, CNRS


  IGF-Nord 225

  04 34 35 93 13

 

Li Xue
Chercheur CDD, CNRS


  IGF Nord 216a

  04 34 35 92 78

 


Major publications

  • Scholler P, Nevoltris D, de Bundel D, Bossi S, Rovira Algans X, Møller TC, El Moustaine D, Moreno D, Blanc E, Fabre L, McLean H, Dupuis E, Valjent E, Mathis G, Daniel H, Trinquet E, Baty D, Chames P, Rondard P, Pin J-P (2017) Allosteric nanobodies reveal a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. Nat Commun:in press.

  • Scholler P, Moreno-Delgado d, Lecat-Guillet N, Doumazane E, Monnier C, Charrier-Savournin F, Fabre L, Chouvet C, Soldevila S, Lamarque L, Donsimoni G, Roux T, Zwier JM, Trinquet E, Rondard P, Pin J-P (2017) HTS compatible FRET-based conformational sensors clarify membrane receptor activation. Nat Chem Biol 13:372-380.

  • Moreno Delgado D, Møller TC, Ster J, Giraldo J, Maurel D, Rovira X, Scholler P, Zwier JM, Perroy J, Durroux T, Trinquet E, Prezeau L, Rondard P, Pin JP (2017) Pharmacological evidence for a metabotropic glutamate receptor heterodimer in neuronal cells. Elife 6.

  • Zussy C, Gómez-Santacana X, Rovira X, De Bundel D, Ferrazzo S, Bosch D, Asede D, Malhaire F, Acher F, Giraldo J, Valjent E, Ehrlich I, Ferraguti F, Pin JP, Llebaria A, Goudet C (2016) Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4. Molecular Psychiatry

  • Comps-Agrar L, Kniazeff J, Brock C, Trinquet E, Pin J-P (2012) Stability of GABAB receptor oligomers revealed by dual TR-FRET and drug-induced cell surface targeting. FASEB J 26:3430-3439.

 

 

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