...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuron >The Subtype of GluN2 C-terminal Domain Determines the Response to Excitotoxic Insults
【24h】

The Subtype of GluN2 C-terminal Domain Determines the Response to Excitotoxic Insults

机译：GluN2 C末端域的亚型决定了对兴奋性毒性反应的反应。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

It is currently unclear whether the GluN2 subtype influences NMDA receptor (NMDAR) excitotoxicity. We report that the toxicity of NMDAR-mediated Ca 2+ influx is differentially controlled by the cytoplasmic C-terminal domains of GluN2B (CTD 2B) and GluN2A (CTD 2A). Studying the effects of acute expression of GluN2A/2B-based chimeric subunits with reciprocal exchanges of their CTDs revealed that CTD 2B enhances NMDAR toxicity, compared to CTD 2A. Furthermore, the vulnerability of forebrain neurons in vitro and in vivo to NMDAR-dependent Ca 2+ influx is lowered by replacing the CTD of GluN2B with that of GluN2A by targeted exon exchange in a mouse knockin model. Mechanistically, CTD 2B exhibits stronger physical/functional coupling to the PSD-95-nNOS pathway, which suppresses protective CREB activation. Dependence of NMDAR excitotoxicity on the GluN2 CTD subtype can be overcome by inducing high levels of NMDAR activity. Thus, the identity (2A versus 2B) of the GluN2 CTD controls the toxicity dose-response to episodes of NMDAR activity.
机译：目前尚不清楚GluN2亚型是否影响NMDA受体（NMDAR）兴奋性毒性。我们报告NMDAR介导的Ca 2 +涌入的毒性是由GluN2B（CTD 2B）和GluN2A（CTD 2A）的胞质C末端域差异控制的。研究与它们的CTD相互交换的基于GluN2A / 2B的嵌合亚基的急性表达的影响，发现与CTD 2A相比，CTD 2B增强NMDAR毒性。此外，在小鼠敲入模型中，通过靶向外显子交换将GluN2B的CTD替换为GluN2A的CTD，可以降低NMDAR依赖性Ca 2+流入的前脑神经元在体内和体外的脆弱性。从机理上讲，CTD 2B与PSD-95-nNOS途径表现出更强的物理/功能偶联，从而抑制了CREB的保护性激活。 NMDAR兴奋性毒性对GluN2 CTD亚型的依赖性可以通过诱导高水平的NMDAR活性来克服。因此，GluN2 CTD的身份（2A对2B）控制了对NMDAR活性发作的毒性剂量反应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号