Hong Wang, Rayan Said, Clémence Nguyen-Vigouroux, Véronique Henriot, Peter Gebhardt, Julien Pernier, Robert Grosse, Christophe Le Clainche
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引用次数: 0
摘要
病灶粘附(FA)可加强其与肌动蛋白细胞骨架的联系以抵抗外力。Talin-vinculin 结合可通过控制肌动蛋白聚合来加强肌动蛋白对 FA 的锚定。然而,目前还不清楚塔林-长春质蛋白复合物的肌动蛋白聚合活性,因为这需要重建控制塔林和长春质蛋白结合的机械和生化激活步骤。通过将动力学和结合测定与 TIRF 显微镜下的单个肌动蛋白丝观察相结合,我们发现,模仿机械拉伸的 talin 和活化的 vinculin 突变体的 talin 和 vinculin 的结合触发了一个有序的机制,在这个机制中,肌动蛋白丝被成核、封盖和释放以伸长。与这些观察结果一致的是,在共同表达相同组成型突变体的细胞中进行的 FRAP 实验显示,应力纤维的生长速度加快。我们的研究结果表明,在各种生化和机械因素的作用下,FAs 中肌动蛋白组装的调节机制是多变的。
Talin and vinculin combine their activities to trigger actin assembly
Focal adhesions (FAs) strengthen their link with the actin cytoskeleton to resist force. Talin-vinculin association could reinforce actin anchoring to FAs by controlling actin polymerization. However, the actin polymerization activity of the talin-vinculin complex is not known because it requires the reconstitution of the mechanical and biochemical activation steps that control the association of talin and vinculin. By combining kinetic and binding assays with single actin filament observations in TIRF microscopy, we show that the association of talin and vinculin mutants, mimicking mechanically stretched talin and activated vinculin, triggers a sequential mechanism in which filaments are nucleated, capped and released to elongate. In agreement with these observations, FRAP experiments in cells co-expressing the same constitutive mutants of talin and vinculin revealed accelerated growth of stress fibers. Our findings suggest a versatile mechanism for the regulation of actin assembly in FAs subjected to various combinations of biochemical and mechanical cues.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.