通过YAP/TAZ和TEAD对哺乳动物昼夜钟的机械控制
Juan F Abenza1,2, Leone Rossetti1, Malèke Mouelhi1
1Institute for Bioengineering of Catalonia , The Barcelona Institute for Science and Technology , Barcelona, Spain.
The Journal of cell biology
|June 28, 2023
概括
细胞昼夜时钟是由YAP/TAZ核水平机械调节的. 这种机械生物学的调节影响了时钟基因,可以解释衰老和癌症中的昼夜节律障碍.
科学领域:
- 细胞生物学 细胞生物学
- 时间生物学 时间生物学
- 机械生物学 机械生物学
背景情况:
- 哺乳动物细胞拥有自主昼夜时钟,受到其微观环境的调节.
- 虽然生物化学调节已被理解,但细胞钟的机械调节在很大程度上是未知的.
研究的目的:
- 研究机械线索在调节纤维细胞昼夜钟中的作用.
- 阐明将机械信号与昼夜节律联系起来的分子机制.
主要方法:
- 高通量单细胞昼夜节律分析.
- 控制的机械,生化和遗传乱.
- 对时钟基因表达 (Rev-erbα,Bmal1,Cry1) 和YAP/TAZ定位的分析.
主要成果:
- 纤维细胞的昼夜时钟是通过YAP/TAZ核水平机械调节的.
- YAP/TAZ核转位破坏了Rev-erbα的昼夜振荡.
- 机械调节取决于YAP/TAZ与TEAD的结合,影响Bmal1和Cry1.
结论:
- YAP/TAZ-TEAD相互作用调节纤维细胞昼夜钟的机械生物学调节.
- 升高的YAP/TAZ活性可能会在癌症和衰老等疾病中损害昼夜节律.
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