Institut de Biologia Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Baldiri Reixac, 10-12, Barcelona 08028, Spain.
Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Dev Cell. 2019 Aug 5;50(3):313-326.e5. doi: 10.1016/j.devcel.2019.07.007. Epub 2019 Jul 25.
Tricellular adherens junctions are points of high tension that are central to the rearrangement of epithelial cells. However, the molecular composition of these junctions is unknown, making it difficult to assess their role in morphogenesis. Here, we show that Sidekick, an immunoglobulin family cell adhesion protein, is highly enriched at tricellular adherens junctions in Drosophila. This localization is modulated by tension, and Sidekick is itself necessary to maintain normal levels of cell bond tension. Loss of Sidekick causes defects in cell and junctional rearrangements in actively remodeling epithelial tissues like the retina and tracheal system. The adaptor proteins Polychaetoid and Canoe are enriched at tricellular adherens junctions in a Sidekick-dependent manner; Sidekick functionally interacts with both proteins and directly binds to Polychaetoid. We suggest that Polychaetoid and Canoe link Sidekick to the actin cytoskeleton to enable tricellular adherens junctions to maintain or transmit cell bond tension during epithelial cell rearrangements.
三细胞黏附连接点是张力集中的部位,对于上皮细胞的重排至关重要。然而,这些连接点的分子组成尚不清楚,这使得评估它们在形态发生中的作用变得困难。在这里,我们发现在果蝇中,免疫球蛋白家族细胞黏附蛋白 Sidekick 高度富集在三细胞黏附连接点。这种定位受张力调节,并且 Sidekick 本身对于维持正常的细胞黏附张力水平是必需的。缺失 Sidekick 会导致活跃重塑的上皮组织(如视网膜和气管系统)中的细胞和连接重排缺陷。衔接蛋白 Polychaetoid 和 Canoe 以 Sidekick 依赖的方式富集在三细胞黏附连接点;Sidekick 与这两种蛋白在功能上相互作用,并直接与 Polychaetoid 结合。我们认为,Polychaetoid 和 Canoe 将 Sidekick 与肌动蛋白细胞骨架连接起来,使三细胞黏附连接点在上皮细胞重排过程中能够维持或传递细胞黏附张力。