Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD.
J Cell Biol. 2019 Oct 7;218(10):3472-3488. doi: 10.1083/jcb.201902067. Epub 2019 Sep 3.
How mammalian cells regulate their physical size is currently poorly understood, in part due to the difficulty in accurately quantifying cell volume in a high-throughput manner. Here, using the fluorescence exclusion method, we demonstrate that the mechanosensitive transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are regulators of single-cell volume. The role of YAP/TAZ in volume regulation must go beyond its influence on total cell cycle duration or cell shape to explain the observed changes in volume. Moreover, for our experimental conditions, volume regulation by YAP/TAZ is independent of mTOR. Instead, we find that YAP/TAZ directly impacts the cell division volume, and YAP is involved in regulating intracellular cytoplasmic pressure. Based on the idea that YAP/TAZ is a mechanosensor, we find that inhibiting myosin assembly and cell tension slows cell cycle progression from G1 to S. These results suggest that YAP/TAZ may be modulating cell volume in combination with cytoskeletal tension during cell cycle progression.
目前，人们对哺乳动物细胞如何调节其物理大小知之甚少，部分原因是难以高通量地准确量化细胞体积。在这里，我们使用荧光排除法证明，机械敏感转录调节剂 YAP（Yes 相关蛋白）和 TAZ（具有 PDZ 结合基序的转录共激活因子）是单细胞体积的调节剂。YAP/TAZ 在体积调节中的作用必须超出其对总细胞周期持续时间或细胞形状的影响，才能解释所观察到的体积变化。此外，对于我们的实验条件，YAP/TAZ 的体积调节独立于 mTOR。相反，我们发现 YAP/TAZ 直接影响细胞分裂体积，YAP 参与调节细胞内细胞质压力。基于 YAP/TAZ 是机械感受器的观点，我们发现抑制肌球蛋白组装和细胞张力会减缓细胞从 G1 到 S 的周期进程。这些结果表明，YAP/TAZ 可能在细胞周期进程中结合细胞骨架张力来调节细胞体积。
