Molecular and Cellular Anatomy, University of Regensburg, 93053 Regensburg, Germany.
J Cell Biol. 2012 Nov 12;199(4):685-98. doi: 10.1083/jcb.201206064. Epub 2012 Nov 5.
The assembly and consolidation of the adherens junctions (AJs) are key events in the establishment of an intact epithelium. However, AJs are further modified to obtain flexibility for cell migration and morphogenetic movements. Intact AJs in turn are a prerequisite for the establishment and maintenance of apical-basal polarity in epithelial cells. In this study, we report that the conserved PDZ (PSD95, Discs large, ZO-1) domain-containing protein PATJ (Pals1-associated tight junction protein) was not per se crucial for the maintenance of apical-basal polarity in Drosophila melanogaster epithelial cells but rather regulated Myosin localization and phosphorylation. PATJ directly bound to the Myosin-binding subunit of Myosin phosphatase and decreased Myosin dephosphorylation, resulting in activated Myosin. Thereby, PATJ supports the stability of the Zonula Adherens. Notably, weakening of AJ in a PATJ mutant epithelium led first to a loss of Myosin from the AJ, subsequently to a disassembly of the AJ, and finally, to a loss of apical-basal polarity and disruption of the tissue.
黏着连接（AJs）的组装和整合是建立完整上皮组织的关键事件。然而，AJs 进一步被修饰以获得细胞迁移和形态发生运动的灵活性。完整的 AJs 反过来又是上皮细胞中建立和维持顶底极性的前提条件。在这项研究中，我们报告说，保守的 PDZ（PSD95、Discs large、ZO-1）结构域包含蛋白 PATJ（Pals1 相关紧密连接蛋白）本身对于维持果蝇上皮细胞的顶底极性并不是至关重要的，而是调节肌球蛋白的定位和磷酸化。PATJ 直接与肌球蛋白磷酸酶的肌球蛋白结合亚基结合，减少肌球蛋白去磷酸化，导致肌球蛋白激活。因此，PATJ 支持 Zonula Adherens 的稳定性。值得注意的是，在 PATJ 突变上皮组织中 AJ 的弱化首先导致肌球蛋白从 AJ 中丢失，随后导致 AJ 的解体，最终导致顶底极性的丧失和组织的破坏。
