EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner.
EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner.
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DOI：
10.1523/jneurosci.0282-11.2011
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发表时间：
2011-04-06
期刊：
影响因子：
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通讯作者：
Dalva MB
中科院分区：
文献类型：
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作者：
Nolt MJ;Lin Y;Hruska M;Murphy J;Sheffler-Colins SI;Kayser MS;Passer J;Bennett MV;Zukin RS;Dalva MB
n -甲基- d -天冬氨酸受体（NMDARs）定位和功能的动态调控对突触发育和功能至关重要。突触中NMDAR亚基的组成和定位受到严格调控，并能影响单个突触对刺激反应的持久变化能力。在这里，我们研究了EphB2（一种结合并磷酸化NMDAR的受体酪氨酸激酶）控制NMDAR亚基定位和突触功能的机制。我们发现，在成熟神经元中，EphB2的表达水平调节突触中NMDARs的数量，EphB的激活降低了含nr2b的NMDARs的Ca2+依赖性脱敏。EphBs是增强成熟神经元突触中含有nr2b的NMDARs定位所必需的；缺乏EphB1-3的三重EphB敲除小鼠表现出NMDAR表面表达的稳态上调和对突触位点的适当靶向性丧失。这些发现表明，在成熟的神经系统中，EphBs是NMDARs突触定位的关键调节因子。
Dynamic regulation of the localization and function of N-methyl-D-aspartate receptors (NMDARs) is critical for synaptic development and function. The composition and localization of NMDAR subunits at synapses are tightly regulated, and can influence the ability of individual synapses to undergo long-lasting changes in response to stimuli. Here we examine mechanisms by which EphB2, a receptor tyrosine kinase that binds and phosphorylates NMDARs, controls NMDAR subunit localization and function at synapses. We find that in mature neurons, EphB2 expression levels regulate the amount of NMDARs at synapses, and EphB activation decreases Ca2+-dependent desensitization of NR2B-containing NMDARs. EphBs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple EphB knockout mice lacking EphB1-3 exhibit homeostatic upregulation of NMDAR surface expression and loss of proper targeting to synaptic sites. These findings demonstrate that in the mature nervous system, EphBs are key regulators of the synaptic localization of NMDARs.