Mechanotransduction is a process by which cells sense the mechanical properties of their surrounding environment and adapt accordingly to perform cellular functions such as adhesion, migration and differentiation. Integrin-mediated focal adhesions are major sites of mechanotransduction and their connection with the actomyosin network is crucial for mechanosensing as well as for the generation and transmission of forces onto the substrate. Despite having emerged as major regulators of cell adhesion and migration, the contribution of microtubules to mechanotransduction still remains elusive. Here, we show that talin- and actomyosin-dependent mechanosensing of substrate rigidity controls microtubule acetylation (a tubulin post-translational modification) by promoting the recruitment of α-tubulin acetyltransferase 1 (αTAT1) to focal adhesions. Microtubule acetylation tunes the mechanosensitivity of focal adhesions and Yes-associated protein (YAP) translocation. Microtubule acetylation, in turn, promotes the release of the guanine nucleotide exchange factor GEF-H1 from microtubules to activate RhoA, actomyosin contractility and traction forces. Our results reveal a fundamental crosstalk between microtubules and actin in mechanotransduction that contributes to mechanosensitive cell adhesion and migration.

机械转导是细胞感知周围环境的机械特性并相应地适应以执行细胞功能如粘附、迁移和分化的过程。整合素介导的粘着斑是机械传导的主要位点，它们与肌动球蛋白网络的连接对于机械传感以及力的产生和传递到基板上至关重要。尽管已成为细胞粘附和迁移的主要调节剂，但微管对机械转导的贡献仍然难以捉摸。在这里，我们表明，依赖于 talin 和肌动球蛋白的底物刚性机械传感通过促进 α-微管蛋白乙酰转移酶 1 (αTAT1) 募集到粘着斑来控制微管乙酰化（微管蛋白翻译后修饰）。微管乙酰化调节粘着斑的机械敏感性和 Yes 相关蛋白 (YAP) 易位。反过来，微管乙酰化促进鸟嘌呤核苷酸交换因子 GEF-H1 从微管中释放，从而激活 RhoA、肌动球蛋白收缩力和牵引力。我们的结果揭示了微管和肌动蛋白在机械转导中的基本串扰，这有助于机械敏感细胞粘附和迁移。