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Involvement of NMDAR2A tyrosine phosphorylation in depression‐related behaviour
Author(s) -
Taniguchi Sachiko,
Nakazawa Takanobu,
Tanimura Asami,
Kiyama Yuji,
Tezuka Tohru,
Watabe Ayako M,
Katayama Norikazu,
Yokoyama Kazumasa,
Inoue Takeshi,
IzumiNakaseko Hiroko,
Kakuta Shigeru,
Sudo Katsuko,
Iwakura Yoichiro,
Umemori Hisashi,
Inoue Takafumi,
Murphy Niall P,
Hashimoto Kouichi,
Kano Masanobu,
Manabe Toshiya,
Yamamoto Tadashi
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.300
Subject(s) - phosphorylation , nmda receptor , biology , tyrosine phosphorylation , long term depression , glutamate receptor , ionotropic effect , tyrosine , striatum , microbiology and biotechnology , neuroscience , receptor , ampa receptor , biochemistry , dopamine
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.