局部翻译的mTOR控制了神经损伤中的轴突局部翻译
Marco Terenzio1, Sandip Koley1, Nitzan Samra1
1Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
Science (New York, N.Y.)
|March 24, 2018
概括
在受伤后,mTOR mRNA在轴突中的局部翻译启动蛋白质合成. 这一由核素和mTOR调节的过程对于神经元的生存和细胞内信号传递至关重要.
科学领域:
- 神经科学
- 分子生物学
- 细胞生物学
背景情况:
- 神经损伤会触发复杂的细胞反应,包括蛋白质合成的变化.
- 轴突内的局部蛋白质合成对于神经元的修复和生存至关重要.
- 在轴突蛋白质合成和损伤反应中,拉巴胺素的机械标 (mTOR) 的作用尚不完全理解.
研究的目的:
- 研究受伤轴突中局部蛋白质合成启动的机制.
- 确定拉巴胺素机械性标 (mTOR) 在轴突内部调节局部翻译中的作用.
- 阐明mRNA局部化对轴突修复和神经元存活的贡献.
主要方法:
- 使用针对性删除mTOR 3'未翻译区域 (3'UTR) 的小鼠模型.
- 在轴突中使用药理抑制mTOR.
- 研究了通过核素将mTORmRNA输入轴突的过程.
- 在受伤的轴突中评估mTOR,importinβ1和STAT3的蛋白质水平.
主要成果:
- 在受伤的轴突中通过局部mTORmRNA翻译激活和上调 mTOR (拉巴胺素的机械标).
- 核素促进了mTORmRNA的轴突运输.
- mTOR调节自身的翻译和逆行损伤信号分子的翻译 (进口β1,STAT3).
- 删除mTOR 3'UTR或药物抑制轴突mTOR会减少神经损伤后的局部转化和神经生存.
结论:
- mRNA局部化为mTOR途径提供时空控制,控制局部翻译和细胞内信号传递.
- 在神经损伤后,局部mTOR激活对于轴突修复和自身感应神经元的存活至关重要.
- 针对本地蛋白质合成途径为神经元损伤提供了潜在的治疗策略.
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