Adhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion.
Adhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion.
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DOI：
10.1038/s41467-020-20563-9
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发表时间：
2021-01-15
影响因子：
16.6
通讯作者：
Ladoux B
中科院分区：
文献类型：
--
作者：
Le AP;Rupprecht JF;Mège RM;Toyama Y;Lim CT;Ladoux B
细胞凋亡在维持上皮细胞内环境稳定中起重要作用。目前的文献支持上皮细胞通过在邻近细胞中形成超细胞肌动球蛋白荷包串来对挤压做出反应。然而，其他肌动蛋白结构是否有助于挤出以及这些结构产生的力如何整合尚不清楚。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的细胞中重组。早期存在的基底板状伪足突起参与了挤压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。一个理论模型集成了这些细胞mechanosensitive组件来解释为什么一个双模式的机制，它结合了板状伪足突起和荷包收缩，导致更有效的挤出比一个单一的模式机制。在这项工作中，我们提供了机制的洞察挤压，一个重要的上皮稳态过程。细胞挤出调节单层细胞密度，并且在维持上皮完整性中至关重要，这在体内平衡、发育和癌症进展中具有意义。在这里，作者描述了单层如何整合来自组织力学、细胞-细胞粘附、细胞-基质粘附和细胞骨架协调细胞挤出的机械信号。
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. Cell extrusion regulates monolayer cell density and is critical in maintaining epithelia integrity, which has implications in homeostasis, development, and cancer progression. Here the authors describe how monolayer integrate mechanical signals from tissue mechanics, cell-cell adhesion, cell-substrate adhesion and cytoskeleton coordinate cell extrusion.
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影响因子：
19.6
作者：
Brugués A;Anon E;Conte V;Veldhuis JH;Gupta M;Colombelli J;Muñoz JJ;Brodland GW;Ladoux B;Trepat X
通讯作者：
Trepat X
影响因子：
7.2
作者：
Andrade, Daniel;Rosenblatt, Jody
通讯作者：
Rosenblatt, Jody
影响因子：
9.2
作者：
Abreu-Blanco, Maria Teresa;Verboon, Jeffrey M.;Parkhurst, Susan M.
通讯作者：
Parkhurst, Susan M.
影响因子：
4
作者：
Kuipers, Dorothy;Mehonic, Aida;Gale, Jonathan E.
通讯作者：
Gale, Jonathan E.
DOI：
10.1073/pnas.0408482102
发表时间：
2005-02-15
影响因子：
11.1
作者：
du Roure, O;Saez, A;Ladoux, B
通讯作者：
Ladoux, B