TrkB receptor interacts with mGlu<sub>2</sub> receptor and mediates antipsychotic-like effects of mGlu<sub>2</sub> receptor activation in the mouse.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38277461.
- Also identified by DOI 10.1126/sciadv.adg1679 and PMC identifier 10816717.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Metabotropic glutamate receptor 2 (mGlu<sub>2</sub>) attracts particular attention as a possible target for a new class of antipsychotics. However, the signaling pathways transducing the effects of mGlu<sub>2</sub> in the brain remain poorly characterized. Here, we addressed this issue by identifying native mGlu<sub>2</sub> interactome in mouse prefrontal cortex. Nanobody-based affinity purification and mass spectrometry identified 149 candidate mGlu<sub>2</sub> partners, including the neurotrophin receptor TrkB. The later interaction was confirmed both in cultured cells and prefrontal cortex. mGlu<sub>2</sub> activation triggers phosphorylation of TrkB on Tyr<sup>816</sup> in primary cortical neurons and prefrontal cortex. Reciprocally, TrkB stimulation enhances mGlu<sub>2</sub>-operated G<sub>i/o</sub> 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<sub>2</sub>, which is key to the behavioral response to glutamatergic antipsychotics.
Medical subject headings
- Antipsychotic Agents