Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner.
Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner.
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DOI：
10.1016/j.cub.2013.01.009
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发表时间：
2013-02-18
期刊：
影响因子：
9.2
通讯作者：
Ballestrem, Christoph
中科院分区：
文献类型：
--
作者：
Carisey, Alex;Tsang, Ricky;Greiner, Alexandra M.;Nijenhuis, Nadja;Heath, Nikki;Nazgiewicz, Alicja;Kemkemer, Ralf;Derby, Brian;Spatz, Joachim;Ballestrem, Christoph
细胞通过与细胞内肌动蛋白骨架连接的粘附受体（整合素）通过一个复杂的调节蛋白网络感知细胞外环境，这些调节蛋白共同形成局灶粘附（FAs）。这些传感单元如何被调节的分子基础，它们如何参与机械刺激的转导，以及这如何导致FAs的时空协调尚不清楚。在这里，我们表明，通过与talin-integrin复合物和F-actin的联系，血管蛋白调节了从细胞外基质到肌动球蛋白机制的机械信号的传递。我们证明了血管蛋白与talin-integrin复合物的相互作用驱动核心FA成分的募集和释放。血管蛋白的激活状态本身受力调节，正如我们的观察所强调的那样，血管蛋白定位于FAs依赖于肌动球蛋白的收缩。利用多种血管蛋白突变体，我们建立了细胞-基质粘附网络的哪些组成部分通过与血管蛋白的直接和间接关联进行协调。此外，通过循环拉伸，我们证明了血管蛋白在细胞外机械刺激的传递中起着关键作用，导致细胞极性的重组。特别重要的是肌动蛋白结合的尾部区域，没有它，细胞在响应循环拉伸时的再极化能力会受到干扰。总的来说，我们的数据促进了一个模型，即血管蛋白控制细胞内和细胞外机械信号的传递，这些信号对FAs的时空组装、拆卸和重组很重要，以协调极化的细胞运动。►细胞内张力是维持肌动蛋白黏附的必要条件►血管蛋白的活性稳定了talin-integrin复合物并增加了细胞黏附►血管蛋白通过talin-integrin复合物协调FA蛋白的释放►血管蛋白通过与肌动蛋白的连接协调拉伸诱导的细胞极化
Cells sense the extracellular environment using adhesion receptors (integrins) linked to the intracellular actin cytoskeleton through a complex network of regulatory proteins that, all together, form focal adhesions (FAs). The molecular basis of how these sensing units are regulated, how they are implicated in transducing mechanical stimuli, and how this leads to a spatiotemporal coordination of FAs is unclear. Here we show that vinculin, through its links to the talin-integrin complex and F-actin, regulates the transmission of mechanical signals from the extracellular matrix to the actomyosin machinery. We demonstrate that the vinculin interaction with the talin-integrin complex drives the recruitment and release of core FA components. The activation state of vinculin is itself regulated by force, as underscored by our observation that vinculin localization to FAs is dependent on actomyosin contraction. Using a variety of vinculin mutants, we establish which components of the cell-matrix adhesion network are coordinated through direct and indirect associations with vinculin. Moreover, using cyclic stretching, we demonstrate that vinculin plays a key role in the transmission of extracellular mechanical stimuli leading to the reorganization of cell polarity. Of particular importance is the actin-binding tail region of vinculin, without which the cell’s ability to repolarize in response to cyclic stretching is perturbed. Overall our data promote a model whereby vinculin controls the transmission of intracellular and extracellular mechanical cues that are important for the spatiotemporal assembly, disassembly, and reorganization of FAs to coordinate polarized cell motility. ► Intracellular tension is required to maintain vinculin in focal adhesions ► Vinculin activity stabilizes the talin-integrin complex and increases cell adhesion ► Vinculin coordinates the release of FA proteins through the talin-integrin complex ► Vinculin coordinates stretch-induced cell polarization via its link to actin
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