| First Author | Philibert CE | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 4 | Pages | eadg1679 |
| PubMed ID | 38277461 | Mgi Jnum | J:347270 |
| Mgi Id | MGI:7578451 | Doi | 10.1126/sciadv.adg1679 |
| Citation | Philibert CE, et al. (2024) TrkB receptor interacts with mGlu(2) receptor and mediates antipsychotic-like effects of mGlu(2) receptor activation in the mouse. Sci Adv 10(4):eadg1679 |
| abstractText | Metabotropic glutamate receptor 2 (mGlu(2)) attracts particular attention as a possible target for a new class of antipsychotics. However, the signaling pathways transducing the effects of mGlu(2) in the brain remain poorly characterized. Here, we addressed this issue by identifying native mGlu(2) interactome in mouse prefrontal cortex. Nanobody-based affinity purification and mass spectrometry identified 149 candidate mGlu(2) partners, including the neurotrophin receptor TrkB. The later interaction was confirmed both in cultured cells and prefrontal cortex. mGlu(2) activation triggers phosphorylation of TrkB on Tyr(816) in primary cortical neurons and prefrontal cortex. Reciprocally, TrkB stimulation enhances mGlu(2)-operated G(i/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 mGlu(2), which is key to the behavioral response to glutamatergic antipsychotics. |
