...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Cytoplasmic localization of amyotrophic lateral sclerosis-related TDP-43 proteins modulates stress granule formation
【24h】

Cytoplasmic localization of amyotrophic lateral sclerosis-related TDP-43 proteins modulates stress granule formation

机译：肌萎缩侧面硬化和化学相关TDP-43蛋白的细胞质定位调节应激颗粒形成

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

TDP-43 is an RNA/DNA-binding protein associated with amyotrophic lateral sclerosis (ALS). Under pathological conditions, TDP-43 exported from the nucleus accumulates in the cytoplasm, forming inclusion bodies. However, the molecular mechanisms that contribute to such aggregation are unclear. The pathogenic processes that lead to aggregation in ALS were investigated by analysing the effects of wildtype human TDP-43 or with mutations in the nuclear localization sequence (NLS) or those associated with ALS in stress granule formation. TDP-43 (WT, increment NLS or G348C), with or without a GFP-tag, was expressed in SH-SY5Y neuroblastoma or HeLa cells and stress granules induced by oxidative stress or heat shock. Stress granule formation was altered in cells strongly expressing GFP-TDP- increment NLS, or untagged TDP-43- increment NLS in the cytoplasm but not the negative controls, GFP or GFP-UtrCH. In contrast, there was no reduction in stress granule formation by cells that expressed untagged TDP-43 (WT or G348C) in the nucleus upon stress induction. GFP labelling of TDP-43 (WT or G348C) promotes high cytoplasmic expression and nuclear aggregation. Stress granule formation was impaired in cells expressing GFP-TDP-43 (WT or G348C) in the cytoplasm. Overall, these results suggest that stress granule formation may be inhibited by high levels of TDP-43 protein in the cytoplasm. As stress granules serve a protective function, their deregulation may promote neurodegeneration due to an aberrant stress response.
机译：TDP-43是一种与肌萎缩侧索硬化症（ALS）相关的RNA/DNA结合蛋白。在病理条件下，从细胞核输出的TDP-43积聚在细胞质中，形成包涵体。然而，导致这种聚集的分子机制尚不清楚。通过分析野生型人类TDP-43或核定位序列（NLS）突变或与ALS相关的应激颗粒形成的影响，研究了导致ALS聚集的致病过程。TDP-43（WT、增量NLS或G348C）在SH-SY5Y神经母细胞瘤或HeLa细胞以及氧化应激或热休克诱导的应激颗粒中表达，无论是否带有GFP标记。在细胞质中强烈表达GFP-TDP-增量NLS或未标记TDP-43-增量NLS的细胞中，应激颗粒的形成发生了改变，但在阴性对照、GFP或GFP-UtrCH中没有改变。相反，在应力诱导下，细胞核中表达未标记TDP-43（WT或G348C）的细胞的应力颗粒形成没有减少。绿色荧光蛋白标记的TDP-43（WT或G348C）促进高细胞质表达和核聚集。在细胞质中表达GFP-TDP-43（WT或G348C）的细胞中，应激颗粒的形成受到损害。总的来说，这些结果表明，细胞质中高水平的TDP-43蛋白可能会抑制应激颗粒的形成。由于应激颗粒具有保护功能，它们的去调节可能会由于异常的应激反应而促进神经退行性变。

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