| First Author | Taniguchi S | Year | 2009 |
| Journal | EMBO J | Volume | 28 |
| Issue | 23 | Pages | 3717-29 |
| PubMed ID | 19834457 | Mgi Jnum | J:155360 |
| Mgi Id | MGI:4413543 | Doi | 10.1038/emboj.2009.300 |
| Citation | Taniguchi S, et al. (2009) Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour. EMBO J 28(23):3717-29 |
| abstractText | Major depressive and bipolar disorders are serious illnesses that affect millions of people. Growing evidence implicates glutamate signalling in depression, though the molecular mechanism by which glutamate signalling regulates depression-related behaviour remains unknown. In this study, we provide evidence suggesting that tyrosine phosphorylation of the NMDA receptor, an ionotropic glutamate receptor, contributes to depression-related behaviour. The NR2A subunit of the NMDA receptor is tyrosine-phosphorylated, with Tyr 1325 as its one of the major phosphorylation site. We have generated mice expressing mutant NR2A with a Tyr-1325-Phe mutation to prevent the phosphorylation of this site in vivo. The homozygous knock-in mice show antidepressant-like behaviour in the tail suspension test and in the forced swim test. In the striatum of the knock-in mice, DARPP-32 phosphorylation at Thr 34, which is important for the regulation of depression-related behaviour, is increased. We also show that the Tyr 1325 phosphorylation site is required for Src-induced potentiation of the NMDA receptor channel in the striatum. These data argue that Tyr 1325 phosphorylation regulates NMDA receptor channel properties and the NMDA receptor-mediated downstream signalling to modulate depression-related behaviour. |
