Nanoscale architecture of cadherin-based cell adhesions.
Nanoscale architecture of cadherin-based cell adhesions.
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DOI：
10.1038/ncb3456
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发表时间：
2017-01
影响因子：
21.3
通讯作者：
Kanchanawong P
中科院分区：
文献类型：
--
作者：
Bertocchi C;Wang Y;Ravasio A;Hara Y;Wu Y;Sailov T;Baird MA;Davidson MW;Zaidel-Bar R;Toyama Y;Ladoux B;Mege RM;Kanchanawong P
动物的多细胞生物需要细胞间接触的动态维持。细胞间连接的钙粘蛋白招募大量蛋白质形成超分子复合物，与肌动蛋白细胞骨架连接并支持力传递。然而，这些结构中的分子组织仍然是未知的。在这里，我们通过超分辨率显微镜绘制了基于钙粘蛋白的粘附中的蛋白质组织，揭示了一个多室纳米级结构，质膜-近端钙粘蛋白-连环蛋白室与肌动蛋白细胞骨架室分离，由含有血管蛋白的界面区桥接。Vinculin的位置由α-catenin决定，激活后，Vinculin可以延伸~ 30 nm，以桥接钙粘蛋白-catenin和肌动蛋白室，同时调节肌动蛋白调节因子、zyxin和VASP的纳米级位置。血管蛋白构象激活需要张力和酪氨酸磷酸化，由Abl激酶和PTP1B磷酸酶调节。这种模块化结构为血管蛋白的机械和生化信号整合提供了一个结构框架，血管蛋白可能以不同的方式参与钙粘蛋白-连环蛋白复合物和肌动球蛋白机制来调节细胞粘附。
Multicellularity in animals requires dynamic maintenance of cell-cell contacts. Intercellularly ligated cadherins recruit numerous proteins to form supramolecular complexes that connect with the actin cytoskeleton and support force transmission. However, the molecular organization within such structures remains unknown. Here we mapped protein organization in cadherin-based adhesions by superresolution microscopy, revealing a multi-compartment nanoscale architecture, with the plasma membrane-proximal cadherin-catenin compartment segregated from the actin cytoskeletal compartment, bridged by an interface zone containing vinculin. Vinculin position is determined by α-catenin, and upon activation, vinculin can extend ˜30 nm to bridge the cadherin-catenin and actin compartments, while modulating the nanoscale positions of the actin regulators, zyxin and VASP. Vinculin conformational activation requires tension and tyrosine phosphorylation, regulated by Abl kinase, and PTP1B phosphatase. Such modular architecture provides a structural framework for mechanical and biochemical signal integration by vinculin, which may differentially engage cadherin-catenin complexes with the actomyosin machinery to regulate cell adhesions.