Eidgenössische Technische Hochschule (ETH) Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
Nat Commun. 2017 Jan 27;8:14348. doi: 10.1038/ncomms14348.
Upon binding to the extracellular matrix protein, fibronectin, αV-class and α5β1 integrins trigger the recruitment of large protein assemblies and strengthen cell adhesion. Both integrin classes have been functionally specified, however their specific roles in immediate phases of cell attachment remain uncharacterized. Here, we quantify the adhesion of αV-class and/or α5β1 integrins expressing fibroblasts initiating attachment to fibronectin (≤120 s) by single-cell force spectroscopy. Our data reveals that αV-class integrins outcompete α5β1 integrins. Once engaged, αV-class integrins signal to α5β1 integrins to establish additional adhesion sites to fibronectin, away from those formed by αV-class integrins. This crosstalk, which strengthens cell adhesion, induces α5β1 integrin clustering by RhoA/ROCK/myosin-II and Arp2/3-mediated signalling, whereas overall cell adhesion depends on formins. The dual role of both fibronectin-binding integrin classes commencing with an initial competition followed by a cooperative crosstalk appears to be a basic cellular mechanism in assembling focal adhesions to the extracellular matrix.
与细胞外基质蛋白纤维连接蛋白结合后，αV 类和 α5β1 整合素触发大型蛋白组装的募集并增强细胞黏附。这两种整合素类别均具有功能特异性，但其在细胞附着的即时阶段的具体作用尚未确定。在这里，我们通过单细胞力谱法定量测定表达纤维连接蛋白的 αV 类和/或 α5β1 整合素的成纤维细胞起始附着至纤维连接蛋白（≤120 秒）的黏附。我们的数据表明，αV 类整合素可以与 α5β1 整合素竞争。一旦结合，αV 类整合素会向 α5β1 整合素发出信号，在远离 αV 类整合素形成的黏附位点处建立与纤维连接蛋白的其他黏附位点。这种加强细胞黏附的串扰会通过 RhoA/ROCK/肌球蛋白 II 和 Arp2/3 介导的信号诱导 α5β1 整合素聚集，而整体细胞黏附则取决于成核蛋白。两种纤维连接蛋白结合整合素类别的双重作用似乎是一种基本的细胞机制，即开始时存在初始竞争，随后是协同串扰，从而将焦点黏附组装到细胞外基质上。
