Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating contractile forces before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be ratcheting mechanisms that drive processive transformations in cell shape. Previous work has shown that force generation is coordinated with endocytic remodeling; however, how ratcheting becomes engaged at specific cell surfaces remains unclear. Here, we report that PtdIns(3,4,5)P₃ is a critical lipid-based cue for ratcheting engagement. The Sbf RabGEF binds to PIP₃, and disruption of PIP₃ reveals a dramatic switching behavior in which medial ratcheting is activated and epithelial cells begin globally constricting apical surfaces. PIP₃ enrichments are developmentally regulated, with mesodermal cells having high apical PIP₃ while germband cells have higher interfacial PIP₃. Finally, we show that JAK/STAT signaling constitutes a second pathway that combinatorially regulates Sbf/Rab35 recruitment. Our results elucidate a complex lipid-dependent regulatory machinery that directs ratcheting engagement in epithelial tissues.

上皮组织中的力产生通常是脉动的，肌动球蛋白网络在循环分解之前产生收缩力。细胞骨架力的这种脉冲性质意味着必须存在驱动细胞形状进行性转变的棘轮机制。以前的工作表明，力的产生与内吞重塑相协调；然而，棘轮作用如何在特定细胞表面起作用仍不清楚。在这里，我们报告 PtdIns(3,4,5)P ₃是棘轮参与的关键脂质线索。Sbf RabGEF 与 PIP _{3结合，PIP 3}的中断揭示了一种戏剧性的转换行为，其中内侧棘轮被激活，上皮细胞开始全局收缩顶端表面。画中画₃富集受发育调节，中胚层细胞具有高顶端 PIP ₃而胚带细胞具有更高的界面 PIP ₃。最后，我们表明 JAK/STAT 信号构成了组合调节 Sbf/Rab35 募集的第二条途径。我们的结果阐明了一种复杂的脂质依赖性调节机制，该机制指导上皮组织的棘轮参与。