NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity
NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity
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DOI：
10.1038/sj.emboj.7601156
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发表时间：
2006-06-21
期刊：
影响因子：
11.4
通讯作者：
Manabe, Toshiya
中科院分区：
文献类型：
--
作者：
Nakazawa, Takanobu;Komai, Shoji;Manabe, Toshiya
神经元蛋白质对多种外界刺激的磷酸化反应是神经回路动态变化的主要机制之一。NMDA受体的NR 2B亚基在脑中被酪氨酸磷酸化，Tyr-1472是其主要磷酸化位点。在这里，我们产生小鼠与敲入突变的Tyr-1472位点苯丙氨酸（Y1472 F），并表明，Tyr-1472磷酸化是必不可少的恐惧学习和杏仁核突触可塑性。基因敲入小鼠表现出与恐惧相关的学习能力受损，杏仁核长时程增强功能降低。NMDA受体介导的CaMKII信号传导在YF/YF小鼠中受损。电子显微镜分析显示，NR 2B亚基的Y1472 F突变体在杏仁核的突触中显示出不正确的定位。因此，我们确定Tyr-1472磷酸化作为恐惧学习和杏仁核突触可塑性的关键介质。
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.