Vinculin controls talin engagement with the actomyosin machinery.
Vinculin controls talin engagement with the actomyosin machinery.
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DOI：
10.1038/ncomms10038
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发表时间：
2015-12-04
影响因子：
16.6
通讯作者：
Ballestrem C
中科院分区：
文献类型：
--
作者：
Atherton P;Stutchbury B;Wang DY;Jethwa D;Tsang R;Meiler-Rodriguez E;Wang P;Bate N;Zent R;Barsukov IL;Goult BT;Critchley DR;Ballestrem C
细胞外基质结合的整合素和细胞内的F-肌动蛋白之间的联系是细胞扩散和迁移所必需的。在这里，我们演示了肌动蛋白结合蛋白talin和vinculin如何合作提供这种联系。通过在talin缺失细胞中表达基于结构的talin突变体，我们表明，虽然talin中的C末端肌动蛋白结合位点(ABS3)是黏附复合体组装所必需的，但中心ABS2是焦点黏附(FA)成熟所必需的。因此，尽管ABS2突变体支持细胞扩散，但细胞缺乏FAs，无法极化，并对周围基质施加减少的力。ABS2被前面机械敏感的纽蛋白结合的R3结构域抑制，R2R3的缺失或结构性活性纽蛋白的表达产生稳定的力非依赖性FAs，尽管细胞的极性受到影响。我们的数据表明了一个模型，即通过ABS3作用于整合素-talin复合体的力促进R3的展开和纽蛋白结合，激活ABS2并将talin锁定到稳定FA的肌动蛋白结合配置中。机械敏感蛋白talin和vinculin介导整合素结合的细胞外基质和肌动蛋白细胞骨架之间的连接。在这里，作者剖析了Talin中两个肌动蛋白结合部位在黏附复合体组装和成熟中的不同作用，这是由vinculin与talin结合调节的。
The link between extracellular-matrix-bound integrins and intracellular F-actin is essential for cell spreading and migration. Here, we demonstrate how the actin-binding proteins talin and vinculin cooperate to provide this link. By expressing structure-based talin mutants in talin null cells, we show that while the C-terminal actin-binding site (ABS3) in talin is required for adhesion complex assembly, the central ABS2 is essential for focal adhesion (FA) maturation. Thus, although ABS2 mutants support cell spreading, the cells lack FAs, fail to polarize and exert reduced force on the surrounding matrix. ABS2 is inhibited by the preceding mechanosensitive vinculin-binding R3 domain, and deletion of R2R3 or expression of constitutively active vinculin generates stable force-independent FAs, although cell polarity is compromised. Our data suggest a model whereby force acting on integrin-talin complexes via ABS3 promotes R3 unfolding and vinculin binding, activating ABS2 and locking talin into an actin-binding configuration that stabilizes FAs. The mechanosensitive proteins talin and vinculin mediate the linkage between integrin-bound extracellular matrix and the actin cytoskeleton. Here the authors dissect distinct roles for two actin-binding sites within talin on adhesion complex assembly and maturation, which are regulated by vinculin binding to talin.