Institut Jacques Monod, Université de Paris and CNRS UMR 7592, Paris, France.
Department of Chemistry, College of Science, Swansea University, Swansea, United Kingdom.
Elife. 2019 Sep 5;8:e46599. doi: 10.7554/eLife.46599.
Adherens junction (AJ) assembly under force is essential for many biological processes like epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and remodeling of AJ. Here, we investigated the role of non-muscle myosin II isoforms (NMIIA and NMIIB) in epithelial junction assembly. NMIIA and NMIIB differentially regulate biogenesis of AJ through association with distinct actin networks. Analysis of junction dynamics, actin organization, and mechanical forces of control and knockdown cells for myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ.
粘着连接(AJ)在力的作用下的组装对于许多生物学过程是必不可少的,如上皮单层弯曲、细胞集体迁移、细胞挤压和伤口愈合。肌动球蛋白细胞骨架在 AJ 的新形成和重塑过程中充当主要的力发生器。在这里,我们研究了非肌肉肌球蛋白 II 同工型(NMIIA 和 NMIIB)在上皮连接组装中的作用。NMIIA 和 NMIIB 通过与不同的肌动蛋白网络的结合,差异调节 AJ 的生物发生。对肌球蛋白的控制和敲低细胞的连接动力学、肌动蛋白组织和机械力进行分析表明,NMIIA 提供了细胞-细胞连接加强和维持所需的机械拉力。NMIIB 参与 E-钙粘蛋白的聚类,维持连接 E-钙粘蛋白复合物和周向肌动蛋白纤维的分支状肌动蛋白层,导致各向异性应力的建立。这些数据揭示了 NMIIA 和 NMIIB 在 AJ 的生物发生和完整性中的意想不到的互补功能。