将NMDA受体信号的突触或突触起源编码和转换到核中
Anna Karpova1, Marina Mikhaylova, Sujoy Bera
1RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Cell
|March 5, 2013
概括
雅各布蛋白作为一个信使,区分突触和超突触N-甲基-D-酸盐受体 (NMDAR) 信号. 它的核运输和酸化状态决定了神经元的生存或死亡,影响了突触可塑性.
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
- 细胞信号传递 细胞信号传递
背景情况:
- N-甲基-D-酸盐受体 (NMDARs) 具有双重作用:突触激活促进生存和可塑性,而突触激活触发神经退行.
- 细胞核区分并响应这些对立的NMDAR信号的机制在很大程度上是未知的.
研究的目的:
- 确定负责转导和区分突触和突触外NMDAR信号到核的蛋白质信使.
- 阐明控制这些NMDAR介导通路的核运输和信号的分子机制.
主要方法:
- 研究了Jacob蛋白在NMDAR信号转导中的作用.
- 利用生物化学试验来分析ERK1/2.2的雅克伯酸化在血清-180中.
- 研究了Jacob贩运对ERK活动及其与α-internexin相互作用的依赖性.
- 评估了雅各布核酸化状态对细胞存活和突触可塑性的影响.
主要成果:
- 雅各布蛋白作为突触与突触NMDAR信号的信使.
- 突触性NMDAR激活,但不是超突触性,通过ERK1/2.2.通过血清-180诱导雅各布酸化.
- 对于从突触点进行远距离的Jacob贩运,ERK活动至关重要.
- 与α-内素的结合可以防止在核过境过程中Jacob/ERK复合物的脱化.
- 雅各布的核酸化状态决定了它在细胞死亡或存活和突触可塑性方面的作用.
结论:
- 雅各布是一个关键的核目标信使,在有益和有害的NMDAR信号之间进行区分.
- 雅各布的酸化依赖的核转移调节了神经元的命运.
- 这一途径为调节神经保护和突触可塑性提供了潜在的目标.
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