YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation.

中文翻译：

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Force 通过调节核孔间的运输来触发 YAP 核进入。

YAP 是一种机械敏感性转录激活剂，在癌症、再生和器官大小控制中起关键作用。在这里，我们展示了施加在细胞核上的力通过减少核孔对分子运输的机械限制来直接驱动 YAP 核易位。暴露于僵硬的环境会导致细胞在细胞核和细胞骨架之间建立机械连接，从而允许通过粘着斑施加的力到达细胞核。然后力传递导致核变平，这会拉伸核孔，降低它们对分子运输的机械阻力，并增加 YAP 核输入。运输的限制进一步受到运输蛋白质的机械稳定性的调节，它决定了 YAP 的主动核转运和小蛋白的被动转运。我们的研究结果揭示了一种直接由核孔介导的机械传感机制，证明了 YAP，但在转录调控中具有潜在的普遍适用性。