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Talin 激活的 vinculin 与分支状的肌动蛋白网络相互作用,从而启动束的形成。

Talin-activated vinculin interacts with branched actin networks to initiate bundles.

机构信息

Department of Biochemistry, University of Zurich, Zurich, Switzerland.

Université Grenoble Alpes, Grenoble, France.

出版信息

Elife. 2020 Nov 13;9:e53990. doi: 10.7554/eLife.53990.

Abstract

Vinculin plays a fundamental role in integrin-mediated cell adhesion. Activated by talin, it interacts with diverse adhesome components, enabling mechanical coupling between the actin cytoskeleton and the extracellular matrix. Here we studied the interactions of activated full-length vinculin with actin and the way it regulates the organization and dynamics of the Arp2/3 complex-mediated branched actin network. Through a combination of surface patterning and light microscopy experiments we show that vinculin can bundle dendritic actin networks through rapid binding and filament crosslinking. We show that vinculin promotes stable but flexible actin bundles having a mixed-polarity organization, as confirmed by cryo-electron tomography. Adhesion-like synthetic design of vinculin activation by surface-bound talin revealed that clustered vinculin can initiate and immobilize bundles from mobile Arp2/3-branched networks. Our results provide a molecular basis for coordinate actin bundle formation at nascent adhesions.

摘要

vinculin 在整合素介导的细胞黏附中起着至关重要的作用。它被 talin 激活后,与多种黏着斑成分相互作用,使细胞骨架与细胞外基质之间实现机械耦联。在此,我们研究了激活的全长 vinculin 与肌动蛋白的相互作用,以及它调控 Arp2/3 复合物介导的分支肌动蛋白网络的组织和动力学的方式。通过表面图案化和光学显微镜实验的组合,我们表明 vinculin 可以通过快速结合和细丝交联来捆绑树突状肌动蛋白网络。我们表明 vinculin 促进稳定但灵活的肌动蛋白束具有混合极性的组织,这一点通过冷冻电镜断层扫描得到了证实。通过表面结合的 talin 模拟 vinculin 的激活,发现簇状 vinculin 可以从移动的 Arp2/3 分支网络中启动和固定束。我们的研究结果为新生黏附处协调的肌动蛋白束形成提供了分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a058/7682986/918a7e932929/elife-53990-fig1.jpg

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