Apoptotic extrusion is crucial in maintaining epithelial homeostasis. Current literature supports that epithelia respond to extrusion by forming a supracellular actomyosin purse-string in the neighbors. However, whether other actin structures could contribute to extrusion and how forces generated by these structures can be integrated are unknown. Here, we found that during extrusion, a heterogeneous actin network composed of lamellipodia protrusions and discontinuous actomyosin cables, was reorganized in the neighboring cells. The early presence of basal lamellipodia protrusion participated in both basal sealing of the extrusion site and orienting the actomyosin purse-string. The co-existence of these two mechanisms is determined by the interplay between the cell-cell and cell-substrate adhesions. A theoretical model integrates these cellular mechanosensitive components to explain why a dual-mode mechanism, which combines lamellipodia protrusion and purse-string contractility, leads to more efficient extrusion than a single-mode mechanism. In this work, we provide mechanistic insight into extrusion, an essential epithelial homeostasis process.

细胞凋亡挤出对于维持上皮稳态至关重要。目前的文献支持上皮细胞通过在邻近细胞中形成上细胞肌动球蛋白荷包来对挤压作出反应。然而，其他肌动蛋白结构是否有助于挤压以及如何整合这些结构产生的力尚不清楚。在这里，我们发现在挤压过程中，由片状伪足突起和不连续的肌动球蛋白电缆组成的异质肌动蛋白网络在相邻细胞中重组。基底板状伪足突出的早期存在参与了挤出部位的基底密封和肌动球蛋白荷包的定向。这两种机制的共存是由细胞-细胞和细胞-基质粘附之间的相互作用决定的。理论模型整合了这些细胞机械敏感成分，以解释为什么结合了板状伪足突出和荷包收缩性的双模式机制比单模式机制能产生更有效的挤压。在这项工作中，我们提供了对挤压（一种重要的上皮稳态过程）的机制见解。