DAPK1与NMDA受体NR2B子单元的相互作用调解了中风中脑损伤
Weihong Tu1, Xin Xu, Lisheng Peng
1Department of Neurology and Neuroscience Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA 70112, USA.
Cell
|February 10, 2010
概括
与死亡相关的蛋白激酶1 (DAPK1) 与N-甲基-D-酸盐 (NMDA) 受体NR2B子单元在超突触部位相互作用. 这种相互作用在脑缺血和中风期间调解神经元死亡,提供了潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- N-甲基-D-酸盐 (NMDA) 受体是参与神经元死亡的关键谷氨酸受体.
- 外突触NMDA受体与不可逆转的神经元损伤有关.
研究的目的:
- 研究死亡相关蛋白激酶1 (DAPK1) 在脑缺血期间NMDA受体功能中的作用.
- 阐明DAP1和NMDA受体子单元之间的分子相互作用.
主要方法:
- 大脑缺血的小鼠模型.
- 同免疫沉研究蛋白质复合体的形成.
- 电生理学记录以评估受体通道导电性.
- 在体内给予来阻止蛋白相互作用.
主要成果:
- 大脑缺血将DAPK1招募到成年小鼠的NMDA受体NR2B蛋白质复合体中.
- DAPK1直接与NR2B的C端尾部 (氨基酸1292-1304) 结合.
- DAPK1在Ser-1303的位置上酸化NR2B,增强受体通道导电性和Ca2+) 流入.
- 遗传删除DAPK1或阻断DAPK1-NR2B相互作用可以保护神经元免受缺血损伤.
结论:
- DAPK1在物理和功能上与超突触NMDA受体NR2B子单元相互作用.
- 这种DAPK1-NR2B相互作用是中风引起的神经元损伤的中心调解者.
- 针对这种相互作用可能提供一种神经保护策略,防止缺血性中风.
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