PIN Jean-Philippe

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

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)

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Major publications

Xue, L., Sun, Q., Zhao, H., Rovira, X., Gai, S., He, Q., Pin, J.-P., Liu, J., and Rondard, P. (2019). Rearrangement of the transmembrane domain interfaces associated with the activation of a GPCR hetero-oligomer. Nat Commun 10, 2765.
Scholler, P., Nevoltris, D., de Bundel, D., Bossi, S., Moreno-Delgado, D., Rovira, X., Moller, T.C., El Moustaine, D., Mathieu, M., Blanc, E., McLean, H., Dupuis, E., Mathis, G., Trinquet, E., Daniel, H., Valjent, E., Baty, D., Chames, P., Rondard, P., and Pin, J.P. (2017). Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation. Nat Commun 8, 1967.
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, J.M., Trinquet, E., Rondard, P., and Pin, J.-P. (2017). HTS compatible FRET-based conformational sensors clarify membrane receptor activation. Nat Chem Biol 13, 372-380.
Xue, L., Rovira, X., Scholler, P., Zhao, H., Liu, J., Pin, J.P., and Rondard, P. (2015). Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer. Nat Chem Biol 11, 134-140.
Olofsson, L., Felekyan, S., Doumazane, E., Scholler, P., Fabre, L., Zwier, J.M., Rondard, P., Seidel, C.A., Pin, J.P., and Margeat, E. (2014). Fine tuning of sub-millisecond conformational dynamics controls metabotropic glutamate receptors agonist efficacy. Nat Commun 5, 5206.

Events

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October 2020

9

Stéphane DIEUDONNE

11:00

Salle Pierre Soulages - IGF Sud 2ème, Montpellier , France

Stéphane DIEUDONNE

THESE HATHAICHANOK IMPHENG

13:30

Genopolys, Montpellier , France

HATHAICHANOK IMPHENG

Date : 09 October 2020