蛋白质的机械稳定性调节它们转移到细胞核中的速度
Elvira Infante1, Andrew Stannard1, Stephanie J Board1
1Department of Physics and Randall Centre for Cell and Molecular Biophysics, King's College London, WC2R 2LS, London, UK.
Nature physics
|July 24, 2023
概括
细胞机械力量控制转录因子 (TF) 进口到细胞核. 蛋白质展开调节TF核进口率,影响基因表达和细胞迁移.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 分子生物学分子生物学
背景情况:
- 细胞机械转导依赖于转录因子 (TF) 在核外的转移.
- 通过核孔综合体 (NPC) 将外部机械线索与TF核进口动态联系在一起的确切机制尚不清楚.
研究的目的:
- 研究转录因子的机械性质如何影响它们的核进口率.
- 阐明蛋白质纳米机械稳定性在调节基因表达和细胞过程中的作用.
主要方法:
- 研究了肌动脉相关转录因子A (MRTFA) 的核进口率.
- 评估了MRTFA的纳米机械稳定性与其进口率之间的相关性.
- 通过标记机械耐药蛋白质来操纵MRTFA的机械稳定性.
- 监测SRF介导的MYL9基因表达和细胞迁移.
主要成果:
- MRTFA的核进口率与其纳米机械稳定性相反相关,而不是热力学稳定性.
- 将机械耐药标签附在MRTFA上会降低MYL9基因表达的调节.
- 减少的MRTFA机械稳定性减缓了细胞迁移.
- 该NPC作为一个机械传感器,检测力量低至~10 pN.
结论:
- 蛋白质的机械展开是通过NPC核转位率的关键调节者.
- 该NPC的功能作为一个敏感的机械传感器.
- 调节TF机械稳定性为控制基因表达提供了一种新的方法.
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