Details

Autor(en) / Beteiligte

• Philibert, Clémentine Eva
• Disdier, Candice
• Lafon, Pierre-André
• Bouyssou, Alexandre
• Oosterlaken, Mathieu
• Galant, Sonya
• Pizzoccaro, Anne
• Tuduri, Pola
• Ster, Jeanne
• Liu, Jianfeng
• Kniazeff, Julie
• Pin, Jean-Philippe
• Rondard, Philippe
• Marin, Philippe
• Vandermoere, Franck

Titel

TrkB receptor interacts with mGlu2 receptor and mediates antipsychotic-like effects of mGlu2 receptor activation in the mouse

Ist Teil von

• Science advances, 2024-01, Vol.10 (4), p.eadg1679-eadg1679

Erscheinungsjahr

2024

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Metabotropic glutamate receptor 2 (mGlu2) attracts particular attention as a possible target for a new class of antipsychotics. However, the signaling pathways transducing the effects of mGlu2 in the brain remain poorly characterized. Here, we addressed this issue by identifying native mGlu2 interactome in mouse prefrontal cortex. Nanobody-based affinity purification and mass spectrometry identified 149 candidate mGlu2 partners, including the neurotrophin receptor TrkB. The later interaction was confirmed both in cultured cells and prefrontal cortex. mGlu2 activation triggers phosphorylation of TrkB on Tyr816 in primary cortical neurons and prefrontal cortex. Reciprocally, TrkB stimulation enhances mGlu2-operated Gi/o protein activation. Furthermore, TrkB inhibition prevents the rescue of behavioral deficits by glutamatergic antipsychotics in phencyclidine-treated mice. Collectively, these results reveal a cross-talk between TrkB and mGlu2, which is key to the behavioral response to glutamatergic antipsychotics.