Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding
Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding
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DOI：
10.1242/jcs.054866
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发表时间：
2009-10-15
影响因子：
4
通讯作者：
Kemkemer, Ralf
中科院分区：
文献类型：
--
作者：
Goldyn, Alexandra M.;Rioja, Borja Aragues;Kemkemer, Ralf
机械力在控制细胞和组织的完整性和功能方面发挥着至关重要的作用。外力被细胞感知并转化为诱导各种反应的信号。为了增加对这些过程的详细了解，我们研究了施加循环拉伸力时粘着斑和细胞骨架的细胞迁移和动态细胞重组。特别令人感兴趣的是微管和 GTP 酶激活在机械转导过程中的作用。我们发现，即使没有微管，粘着斑和肌动蛋白细胞骨架也会在垂直于拉伸力的方向上发生剧烈的重组。相反，我们发现微管方向是由肌动蛋白细胞骨架控制的。使用生化测定和荧光共振能量转移 (FRET) 测量，我们发现 Rac1 和 Cdc42 活性在拉伸时没有变化，而总体 RhoA 活性显着增加，但与完整微管无关。总之，我们证明了力诱导的细胞重组中的关键参与者是粘着斑滑动、RhoA 激活和肌动球蛋白机制。与微管在迁移中的重要性相反，力诱导的细胞重组，包括焦点粘附滑动，独立于动态微管网络。因此，迁移过程中细胞重组的基本分子机制不同于力诱导的细胞重组。
Mechanical forces play a crucial role in controlling the integrity and functionality of cells and tissues. External forces are sensed by cells and translated into signals that induce various responses. To increase the detailed understanding of these processes, we investigated cell migration and dynamic cellular reorganisation of focal adhesions and cytoskeleton upon application of cyclic stretching forces. Of particular interest was the role of microtubules and GTPase activation in the course of mechanotransduction. We showed that focal adhesions and the actin cytoskeleton undergo dramatic reorganisation perpendicular to the direction of stretching forces even without microtubules. Rather, we found that microtubule orientation is controlled by the actin cytoskeleton. Using biochemical assays and fluorescence resonance energy transfer (FRET) measurements, we revealed that Rac1 and Cdc42 activities did not change upon stretching, whereas overall RhoA activity increased dramatically, but independently of intact microtubules. In conclusion, we demonstrated that key players in force-induced cellular reorganisation are focal-adhesion sliding, RhoA activation and the actomyosin machinery. In contrast to the importance of microtubules in migration, the force-induced cellular reorganisation, including focal-adhesion sliding, is independent of a dynamic microtubule network. Consequently, the elementary molecular mechanism of cellular reorganisation during migration is different to the one in force-induced cell reorganisation.