α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism
α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism
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DOI：
10.1242/jcs.163824
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发表时间：
2015-03-15
影响因子：
4
通讯作者：
Gottardi, Cara J.
中科院分区：
文献类型：
--
作者：
Escobar, David J.;Desai, Ridhdhi;Gottardi, Cara J.
钙粘蛋白-连环蛋白粘附复合物是上皮组织稳定性和发育和组织更新过程中动态细胞运动的关键因素。这种复合物是如何被调节来完成这些功能的还没有完全弄清楚。我们在哺乳动物α-E-连环蛋白（也称为连环蛋白α-1）和果蝇α-连环蛋白中鉴定了位于中间（M）区域和羧基末端肌动蛋白结合结构域之间的柔性接头内的几个磷酸化位点。我们表明，这个磷酸化接头（P-接头）是细胞中α-连环蛋白的主要磷酸化区域，并在酪蛋白激酶2和1的共识位点依次修饰。在果蝇中，P-连接子是发育和集体细胞迁移过程中正常α-连环蛋白功能所必需的，尽管在钙粘蛋白-连环蛋白复合物组装或粘附连接形成中没有发现明显的缺陷。在哺乳动物细胞中，使用机械分散测定法，非磷酸化形式的α-连环蛋白显示出细胞间粘附的缺陷。表达磷酸化形式的α-连环蛋白的上皮片在刮伤后表现出更快和更协调的迁移。这些发现表明，在果蝇和哺乳动物细胞中，正常的钙粘蛋白-连环蛋白复合物功能需要α-连环蛋白P-接头的磷酸化和去磷酸化。
The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian alpha E-catenin (also known as catenin alpha-1) and Drosophila alpha-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of alpha-catenin in cells and is sequentially modified at casein kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal alpha-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, non-phosphorylatable forms of alpha-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of alpha-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the alpha-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.