Dynein binds to β-catenin and may tether microtubules at adherens junctions
Dynein binds to β-catenin and may tether microtubules at adherens junctions
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DOI：
10.1038/ncb1001-913
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发表时间：
2001-10-01
影响因子：
21.3
通讯作者：
Holzbaur, ELF
中科院分区：
文献类型：
--
作者：
Ligon, LA;Karki, S;Holzbaur, ELF
微管和肌动蛋白网络之间的相互作用被认为是至关重要的机械和信号事件在细胞皮层。细胞质动力蛋白已被提出介导许多这些相互作用（1-3）。在这里，我们报告说，动力蛋白是本地化的皮质在培养的上皮细胞的adherens交界处，这种定位是敏感的药物，破坏肌动蛋白细胞骨架。动力蛋白被募集以形成细胞之间的接触，在那里它与连接蛋白β-连环蛋白和E-钙粘蛋白一起定位。微管项目对这些早期的接触，我们假设，动力蛋白捕获和系绳微管在这些网站。动力蛋白与β-连环蛋白发生免疫沉淀，生化分析表明动力蛋白直接与β-连环蛋白结合.β-连环蛋白的过表达破坏了动力蛋白的细胞定位，也显著地扰乱了细胞微管阵列的组织。在过度表达β-连环蛋白的细胞中，中心体变得紊乱，微管似乎不再锚定在皮层。这些结果确定了一个新的作用，细胞质动力蛋白在捕获和拴系微管在adherens连接，从而介导的细胞皮质肌动蛋白和微管网络之间的串扰。
Interactions between microtubule and actin networks are thought to be crucial for mechanical and signalling events at the cell cortex. Cytoplasmic dynein has been proposed to mediate many of these interactions(1-3). Here, we report that dynein is localized to the cortex at adherens junctions in cultured epithelial cells and that this localization is sensitive to drugs that disrupt the actin cytoskeleton. Dynein is recruited to developing contacts between cells, where it localizes with the junctional proteins beta -catenin and E-cadherin. Microtubules project towards these early contacts and we hypothesize that dynein captures and tethers microtubules at these sites. Dynein immunoprecipitates with beta -catenin, and biochemical analysis shows that dynein binds directly to beta -catenin. Overexpression of beta -catenin disrupts the cellular localization of dynein and also dramatically perturbs the organization of the cellular microtubule array. In cells overexpressing beta -catenin, the centrosome becomes disorganized and microtubules no longer appear to be anchored at the cortex. These results identify a novel role for cytoplasmic dynein in capturing and tethering microtubules at adherens junctions, thus mediating cross-talk between actin and microtubule networks at the cell cortex.