ALPHA(1)(E)-CATENIN IS AN ACTIN-BINDING AND ACTIN-BUNDLING PROTEIN MEDIATING THE ATTACHMENT OF F-ACTIN TO THE MEMBRANE ADHESION COMPLEX
ALPHA(1)(E)-CATENIN IS AN ACTIN-BINDING AND ACTIN-BUNDLING PROTEIN MEDIATING THE ATTACHMENT OF F-ACTIN TO THE MEMBRANE ADHESION COMPLEX
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DOI：
10.1073/pnas.92.19.8813
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发表时间：
1995-09-12
影响因子：
11.1
通讯作者：
MORROW, JS
中科院分区：
文献类型：
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作者：
RIMM, DL;KOSLOV, ER;MORROW, JS
钙依赖性同型细胞-细胞粘附，由e -钙粘蛋白等分子介导，指导经典上皮细胞极性的建立，并有助于控制迁移、生长和分化。这些作用涉及额外的蛋白质，包括α -和β -连环蛋白（或血小板红蛋白）和p120，以及与皮质肌动蛋白细胞骨架的联系。这些相互作用的分子基础及其相互作用的层次仍然存在争议。我们证明了F-actin和α (E)-catenin之间的直接相互作用，这是E-cadherin或β -catenin的细胞质结构域所不具有的活性。沉降实验和透射电镜直接观察表明，α (1)(E)-catenin在体外以微摩尔亲和力与F-actin结合并捆绑在一起，catenin/G-actin单体比约为1:7 (mol/mol)，重组人β -catenin可以同时与α -catenin/actin复合物结合，但不直接与actin结合。与全长蛋白相比，含有α (1)(E)-catenin氨基末端228个残基或羧基末端447个残基的重组片段单独与肌动蛋白结合，其亲和力降低，而且这两个片段都没有与肌动蛋白结合，除了与血管蛋白相似外，这两个区域都没有与已建立的肌动蛋白结合蛋白同源的序列。总的来说，这些数据表明α (1)(E)-catenin是一种新的肌动蛋白结合和-捆绑蛋白，并支持α (1)(E)-catenin负责在E-cadherin介导的细胞-细胞接触区域组织和系聚肌动蛋白丝的模型。
Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E-cadherin, guides the establishment of classical epithelial cell polarity and contributes to the control of migration, growth, and differentiation, These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton, The molecular basis for these interactions and their hierarchy of interaction remain controversial. We demonstrate a direct interaction between F-actin and alpha(E)-catenin, an activity not shared by either the cytoplasmic domain of E-cadherin or beta-catenin. Sedimentation assays and direct visualization by transmission electron microscopy reveal that alpha(1)(E)-catenin binds and bundles F-actin in vitro with micromolar affinity at a catenin/G-actin monomer ratio of approximate to 1:7 (mol/mol), Recombinant human beta-catenin can simultaneously bind to the alpha-catenin/actin complex but does not bind actin directly. Recombinant fragments encompassing the amino-terminal 228 residues of alpha(1)(E)-catenin or the carboxyl-terminal 447 residues individually bind actin in cosedimentation assays with reduced affinity compared with the full-length protein, and neither fragment bundles actin, Except for similarities to vinculin, neither region contains sequences homologous to established actin-binding proteins, Collectively these data indicate that alpha(1)(E)-catenin is a novel actin binding and -bundling protein and support a model in which alpha(1)(E)-catenin is responsible for organizing and tethering actin filaments at the zones of E-cadherin-mediated cell-cell contact.