Team Philippe MARIN
Neuroproteomics and signalling of brain disorders
Project Regulations and signaling of metabotropic glutamate receptor mGlu2, the target of a new generation of antipsychotics
PRINCIPAL INVESTIGATOR
IGF staff involved
Philippe MARIN
DRCE CNRS
Candice DISDIER
PhD student Inserm
Sonya GALANT
IE CNRS
Our project aims at deciphering in vivo the signaling of metabotropic glutamate receptor mGlu2, the target of a new generation of antipsychotics under clinical trial.
It makes use of high-resolution mass spectrometry and nanobodies (tiny antibodies from Alpaga) in order to characterize in vivo the phosphorylation pattern of the receptor, its interacting proteins and the signaling pathways engaged by its activation.
In fine, this project will provide a better understanding of the mechanism of action of antipsychotics targeting mGlu2 receptor, in particular for symptom resisting to actual antipsychotics.
Amongst the proteins interacting with mGlu2 receptor in the Mouse prefrontal cortex, we identified the receptor TrkB for neurotrophins. The two receptors reciprocally reinforce their canonical signaling. Activity of TrkB is required for the behavioral response of a preclinical mice model to antipsychotics targeting mGlu2 receptor, including their effects on perturbations linked to negative and cognitive symptoms of schizophrenia.
Experimental workflow to functionally characterize mGlu2 receptor interactome
Main publications
• Philibert C., et al. (2024) Sciences Advances. 10(4):eadg1679.
• Schlotter F., et al. (2023) Nucleic Acids Res. 51(7):3357-3374.
• Dos Santos Morais R., et al. (2022) J Mol Biol. 434(19):167760.
• Klimešová K., et al. (2021) Nat Commun. 12(1):3646.
• Abel Y., et al. (2021) Nucleic Acids Res. 49(2):1094-1113.
• Murat S., et al. (2019) Mol. Psychiatry, 24(11):1610-1626.
• Henri J., et al. (2018) Structure. 26(9):1196-1209.e8.
• Cassier E., et al. (2017) Elife, 6:e23777.
• Karaki S., et al. (2014) Mol Cell Proteomics. 13(5):1273-85.
Funding
• Canceropole GSO project SykOnGPCRs 2023-2024. Coordinator
• PRC ANR-22-CE14 MOSDER 2022-2026. Partner
• PRC ANR-21-CE44-0006-02 InteracT 2021-2025. Partner
• PRC ANR-20-CE44-0006 SchizoGlu 2021-2024. Coordinator
• Isite Montpellier UniverSité d’Excellence project NanoSchizo 2018-2022. co-PI
• PRC ANR-10-BLAN-1619 GPCRnet 2011- 2015. Partner
• PRC ANR-2010-BLAN-1601 PhosphoCav 2010-2014. Partner
Collaborations
• Philippe RONDARD / Jean-Philippe PIN (Montpellier)
• Emmanuel BOURINET (Montpellier)
• Céline VERHEGGEN / Edouard BERTRAND (Montpellier)
• Séverine MASSENET (Nancy)
• Sandra LECAT / Frederic SIMONIN (Strasbourg)
• Frédéric JEAN-ALPHONSE / Eric REITER (Tours)
• Evi KOSTENIS (Bonn)
• Ferdinando NICOLETTI (Rome)
• Jiang-Feng LIU (Wuhan)
Alumni
• Thomas Le Cler (Master 1 2023)
• Clémentine Philibert (PhD student 2018-2022)
• Jeanne Espinosa (Master 1 2022)
• Candice Disdier (Master 2 2021)
• Elisabeth Cassier (IE 2009-2017)
• Mathilde Bigot (Master 1 2016)
• Samy Murat (PhD student 2014-2018, Master 1, 2013)
• Samah Karaki (PhD student 2009-2011)
• Jonathan Chapron (Master 1 2015)
• Ramzi EL Fegahli (IR CDD INSERM 2011-2013)
• Madeleine Sugano (IE CDD 2011-2012)
• Alexis Couthier (Master 2 2012)
• Guillaume Blanc (IE CDD 2011)
• Simon Perrin (Master 2 2011)
• Simon Bruno (Master 1 2010)
