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一个进化保存的核糖体救援途径维持了表皮平衡
Kifayathullah Liakath-Ali1,2, Eric W Mills3, Inês Sequeira1
1Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK.
Nature
|April 13, 2018
概括
皮洛塔 (Pelo) 蛋白对于哺乳动物皮肤干细胞的健康至关重要. 皮洛的损失导致细胞生长和分化失控,突出显示其在组织平衡中的作用.
科学领域:
- 分子生物学
- 细胞生物学
- 发育生物学
背景情况:
- 核糖体相关的mRNA质量控制对于蛋白质翻译的忠实性至关重要.
- 虽然在酵母中进行了研究,但其在哺乳动物组织中的作用,特别是干细胞的命运,不太清楚.
- 皮洛塔 (Pelo) 是一种在进化过程中保存的蛋白质,能拯救停滞的核糖体.
研究的目的:
- 调查Pelo在哺乳动物表皮平衡中的作用.
- 确定Pelo删除对小鼠表皮不同干细胞群的影响.
- 阐明Pelo在组织维护中的作用的分子机制.
主要方法:
- 在特定的小鼠表皮干细胞群体 (Lrig1+,Lgr5+,Lgr6+) 中,Pelo的条件删除.
- 细胞增殖,分化和核糖体足迹积累的分析.
- 全球转化率和基因表达的评估.
- 通过使用拉帕来抑制mTOR途径.
主要成果:
- 在Lrig1表达的表皮干细胞中,Pelo的条件删除导致过度增殖和异常分化.
- 皮洛删除导致短核糖体足迹的积累和全球翻译上调.
- 通过mTOR降低调节的转化抑制挽救了表皮表型.
- 皮洛缺失对Lgr5表达干细胞的影响很小,对Lgr6表达干细胞的影响很小.
结论:
- 皮洛塔 (Pelo) 对于维持哺乳动物表皮平衡至关重要.
- 核糖体救援机制在哺乳动物组织维护中起着至关重要的作用.
- 皮洛在表皮的不同干细胞群体上表现出特定的作用.
- 针对转化控制机制可能为组织平衡障碍提供治疗途径.
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