Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours
Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours
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DOI：
10.1242/jcs.138289
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发表时间：
2014-03-15
影响因子：
4
通讯作者：
Gale, Jonathan E.
中科院分区：
文献类型：
--
作者：
Kuipers, Dorothy;Mehonic, Aida;Gale, Jonathan E.
尽管上皮细胞不断地经历有丝分裂和凋亡，但它仍然维持着一种基本的屏障。生物和生物物理机制已经演变成在保持这一屏障的同时清除濒临死亡的细胞。细胞挤出被认为是由相邻细胞形成的多细胞丝状肌动蛋白环驱动的，其收缩为挤出提供机械力，而死亡细胞几乎没有贡献。在这里，我们使用实时共聚焦成像，提供肌动球蛋白动力学的时间分辨三维观察，以揭示死亡细胞在其自身从单层中挤出时的新的机械作用。根据我们的观察，死亡细胞的清除可以细分为两个阶段。第一个阶段是由垂死的细胞驱动的，该阶段通过细胞顶端的皮质收缩F-肌动蛋白和肌球蛋白环的作用对相邻细胞施加张力。第二个阶段与之前的研究一致，是由相邻细胞中的多细胞F-肌动蛋白环驱动的，该环从顶端移动到基底面，以挤压垂死的细胞。至关重要的是，这些数据恢复了濒临死亡的细胞作为细胞挤出的积极物理参与者的地位。
Epithelial cells maintain an essential barrier despite continuously undergoing mitosis and apoptosis. Biological and biophysical mechanisms have evolved to remove dying cells while maintaining that barrier. Cell extrusion is thought to be driven by a multicellular filamentous actin ring formed by neighbouring cells, the contraction of which provides the mechanical force for extrusion, with little or no contribution from the dying cell. Here, we use live confocal imaging, providing time-resolved three-dimensional observations of actomyosin dynamics, to reveal new mechanical roles for dying cells in their own extrusion from monolayers. Based on our observations, the clearance of dying cells can be subdivided into two stages. The first, previously unidentified, stage is driven by the dying cell, which exerts tension on its neighbours through the action of a cortical contractile F-actin and myosin ring at the cell apex. The second stage, consistent with previous studies, is driven by a multicellular F-actin ring in the neighbouring cells that moves from the apical to the basal plane to extrude the dying cell. Crucially, these data reinstate the dying cell as an active physical participant in cell extrusion.