Howard Hughes Medical Institute and Developmental Biology Program, Sloan Kettering Institute, New York, NY.
Weill Cornell Graduate School of Medical Sciences, New York, NY.
J Cell Biol. 2018 Oct 1;217(10):3715-3730. doi: 10.1083/jcb.201801171. Epub 2018 Jul 13.
The reorganization of cells in response to mechanical forces converts simple epithelial sheets into complex tissues of various shapes and dimensions. Epithelial integrity is maintained throughout tissue remodeling, but the mechanisms that regulate dynamic changes in cell adhesion under tension are not well understood. In , planar polarized actomyosin forces direct spatially organized cell rearrangements that elongate the body axis. We show that the LIM-domain protein Ajuba is recruited to adherens junctions in a tension-dependent fashion during axis elongation. Ajuba localizes to sites of myosin accumulation at adherens junctions within seconds, and the force-sensitive localization of Ajuba requires its N-terminal domain and two of its three LIM domains. We demonstrate that Ajuba stabilizes adherens junctions in regions of high tension during axis elongation, and that Ajuba activity is required to maintain cell adhesion during cell rearrangement and epithelial closure. These results demonstrate that Ajuba plays an essential role in regulating cell adhesion in response to mechanical forces generated by epithelial morphogenesis.
细胞对机械力的反应重组成复杂的组织。上皮完整性在组织重塑过程中得以维持，但张力下调节细胞黏附动态变化的机制尚不清楚。在 ，平面极化的肌动球蛋白力指导空间组织的细胞重排，使身体轴伸长。我们发现，在轴伸长过程中，LIM 结构域蛋白 Ajuba 以张力依赖的方式募集到黏着连接。Ajuba 在数秒内定位到肌球蛋白在黏着连接处的聚集点，而 Ajuba 的力敏定位需要其 N 端结构域和三个 LIM 结构域中的两个。我们证明，在轴伸长过程中，Ajuba 在高张力区域稳定黏着连接，并且在细胞重排和上皮闭合过程中维持细胞黏附需要 Ajuba 活性。这些结果表明 Ajuba 在响应上皮形态发生产生的机械力调节细胞黏附中发挥重要作用。
