Department of Oncology and Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Solna, 171 76, Stockholm, Sweden.
Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet and Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Sweden.
Sci Rep. 2017 Aug 8;7(1):7548. doi: 10.1038/s41598-017-07968-1.
The assembly of individual epithelial or endothelial cells into a tight cellular sheet requires stringent control of cell packing and organization. These processes are dependent on the establishment and further integration of cellular junctions, the cytoskeleton and the formation of apical-basal polarity. However, little is known how these subcellular events are coordinated. The (Angiomotin) Amot protein family consists of scaffold proteins that interact with junctional cadherins, polarity proteins and the cytoskeleton. In this report, we have studied how these protein complexes integrate to control cellular shapes consistent with organ function. Using gene-inactivating studies in zebrafish and cell culture systems in vitro, we show that Par3 to be essential for localization of AmotL2 to cellular junctions to associate with VE/E-cadherin and subsequently the organization of radial actin filaments. Our data provide mechanistic insight in how critical processes such as aortic lumen expansion as well as epithelial packing into hexagonal shapes are controlled.
单个上皮或内皮细胞组装成紧密的细胞片层需要严格控制细胞的包装和组织。这些过程依赖于细胞连接的建立和进一步整合、细胞骨架和顶端-基底极性的形成。然而，目前还不太清楚这些亚细胞事件是如何协调的。（血管生成素）Amot 蛋白家族由支架蛋白组成，与细胞连接的钙粘蛋白、极性蛋白和细胞骨架相互作用。在本报告中，我们研究了这些蛋白复合物如何整合以控制与器官功能一致的细胞形状。通过在斑马鱼中的基因失活研究和体外细胞培养系统，我们表明 Par3 对于 AmotL2 定位于细胞连接以与 VE/E-钙粘蛋白结合以及随后的辐射状肌动蛋白丝的组织是必需的。我们的数据提供了机制上的见解，了解了关键过程是如何被控制的，如主动脉腔的扩张以及上皮细胞以六边形的形状包装。
