PIN Jean-Philippe - PRÉZEAU Laurent

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 GABA_B 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 GABA_B receptors and to highlight their therapeutic potential in Parkinson’s disease and pain.

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

Team

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

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.