α-catenin is a molecular switch that binds E-cadherin-β-catenin and regulates actin-filament assembly
α-catenin is a molecular switch that binds E-cadherin-β-catenin and regulates actin-filament assembly
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DOI：
10.1016/j.cell.2005.09.021
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发表时间：
2005-12-02
期刊：
影响因子：
64.5
通讯作者：
Weis, WI
中科院分区：
文献类型：
--
作者：
Drees, F;Pokutta, S;Weis, WI
上皮细胞-细胞连接由黏附蛋白和潜在的肌动蛋白细胞骨架组成，被认为是维持组织结构完整性的稳定结构。与α-连环蛋白通过β-连环蛋白将黏附蛋白E-钙粘蛋白连接到肌动蛋白细胞骨架的观点相反，在随附的论文中，我们报告了α-连环蛋白并不同时与E-钙粘连蛋白-β-连环蛋白和肌动蛋白细丝结合。在这里，我们证明了α-连环蛋白以单体或同源二聚体的形式存在，具有不同的结合性质。单体α-连环蛋白与E-钙粘蛋白-β-连环蛋白结合更强，而二聚体优先与肌动蛋白细丝结合。不同的分子构象与这些不同的结合状态有关，表明α-连环蛋白是一种变构蛋白。值得注意的是，α-连环蛋白通过抑制Arp2/3介导的肌动蛋白聚合直接调节肌动蛋白细丝组织，可能是通过与Arp2/3复合体竞争结合肌动蛋白细丝来实现的。这些结果表明，α-连环蛋白在钙粘附素介导的细胞-细胞黏附部位的肌动蛋白组装和组织的局部调节中发挥了新的作用。
Epithelial cell-cell junctions, organized by adhesion proteins and the underlying actin cytoskeleton, are considered to be stable structures maintaining the structural integrity of tissues. Contrary to the idea that alpha-catenin links the adhesion protein E-cadherin through beta-catenin to the actin cytoskeleton, in the accompanying paper we report that alpha-catenin does not bind simultaneously to both E-cadherin-beta-catenin and actin filaments. Here we demonstrate that alpha-catenin exists as a monomer or a homodimer with different binding properties. Monomeric alpha-catenin binds more strongly to E-cadherin-beta-catenin, whereas the dimer preferentially binds actin filaments. Different molecular conformations are associated with these different binding states, indicating that alpha-catenin is an allosteric protein. Significantly, alpha-catenin directly regulates actin-filament organization by suppressing Arp2/3-mediated actin polymerization, likely by competing with the Arp2/3 complex for binding to actin filaments. These results indicate a new role for alpha-catenin in local regulation of actin assembly and organization at sites of cadherin-mediated cell-cell adhesion.