α-Catenin as a tension transducer that induces adherens junction development
α-Catenin as a tension transducer that induces adherens junction development
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DOI：
10.1038/ncb2055
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发表时间：
2010-06-01
影响因子：
21.3
通讯作者：
Shibata, Mai
中科院分区：
文献类型：
--
作者：
Yonemura, Shigenobu;Wada, Yuko;Shibata, Mai
粘附连接（AJ）由粘附蛋白和底层肌动蛋白细胞骨架组成，可能感知来自相邻细胞的拉力并调节相反的力以维持组织完整性，但其调节机制在分子水平上仍然未知。尽管 α-连环蛋白作为膜和肌动蛋白细胞骨架之间 AJ 形成和功能的直接连接物的可能性已被最小化，但这里我们表明，α-连环蛋白通过 α-连环蛋白构象的力依赖性变化来募集纽蛋白（AJ 的另一种主要肌动蛋白结合蛋白）。我们通过将突变型α-连环蛋白引入细胞并使用体外结合测定，确定了α-连环蛋白分子中力依赖性结合纽蛋白所需的区域。对 α-连环蛋白迁移率进行光漂白分析后的荧光恢复以及以力依赖性方式识别 α-连环蛋白的抗体的存在进一步支持了以下观点：α-连环蛋白是一种张力传感器，可将机械刺激转化为化学反应，从而导致 AJ 的发展。
Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that alpha-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that alpha-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in alpha-catenin conformation. We identified regions in the alpha-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant alpha-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for alpha-catenin mobility and the existence of an antibody recognizing alpha-catenin in a force-dependent manner further supported the notion that alpha-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.