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- Title
NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity.
- Authors
Nakazawa, Takanobu; Komai, Shoji; Watabe, Ayako M; Kiyama, Yuji; Fukaya, Masahiro; Arima-Yoshida, Fumiko; Horai, Reiko; Sudo, Katsuko; Ebine, Kazumi; Delawary, Mina; Goto, June; Umemori, Hisashi; Tezuka, Tohru; Iwakura, Yoichiro; Watanabe, Masahiko; Yamamoto, Tadashi; Manabe, Toshiya
- Abstract
Phosphorylation of neural proteins in response to a diverse array of external stimuli is one of the main mechanisms underlying dynamic changes in neural circuitry. The NR2B subunit of the NMDA receptor is tyrosine-phosphorylated in the brain, with Tyr-1472 its major phosphorylation site. Here, we generate mice with a knockin mutation of the Tyr-1472 site to phenylalanine (Y1472F) and show that Tyr-1472 phosphorylation is essential for fear learning and amygdaloid synaptic plasticity. The knockin mice show impaired fear-related learning and reduced amygdaloid long-term potentiation. NMDA receptor-mediated CaMKII signaling is impaired in YF/YF mice. Electron microscopic analyses reveal that the Y1472F mutant of the NR2B subunit shows improper localization at synapses in the amygdala. We thus identify Tyr-1472 phosphorylation as a key mediator of fear learning and amygdaloid synaptic plasticity.
- Publication
The EMBO journal, 2006, Vol 25, Issue 12, p2867
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601156