An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism
An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism
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DOI：
10.1016/s0960-9822(01)00587-5
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发表时间：
2001-11-27
期刊：
影响因子：
9.2
通讯作者：
Cramer, LP
中科院分区：
文献类型：
--
作者：
Rosenblatt, J;Raff, MC;Cramer, LP
背景：单纯上皮包裹发育中的胚胎和器官。虽然这些上皮细胞仅由一层或两层细胞组成，但它们必须为它们所包裹的组织提供紧密的屏障。在这些简单的上皮细胞内发生的细胞凋亡可能会破坏这一屏障。那么，上皮是如何在不破坏其屏障功能的情况下去除凋亡细胞的呢？结果我们发现，凋亡细胞被挤出一个简单的上皮细胞的协调收缩他们的邻居。肌动蛋白和肌球蛋白的环在凋亡细胞内和在其周围的细胞中形成，并且在活的邻居中形成的环的收缩是凋亡细胞挤出所需的，因为将Rho GT3抑制剂注射到这些细胞中完全阻断挤出。将凋亡的MDCK细胞添加到完整的单层细胞中诱导所接触的细胞中形成肌动蛋白电缆，这表明形成电缆的信号来自垂死细胞。该信号在凋亡过程的非常早期产生，在半胱天冬酶原激活、细胞收缩或磷脂酰丝氨酸暴露之前。值得注意的是，电阻的研究表明，上皮屏障功能的维护，即使大量的垂死的细胞被extruding.Conclusions：我们建议，凋亡细胞的挤出是重要的细胞死亡过程中的上皮屏障功能的保存。我们的研究结果表明，来自垂死细胞的早期信号激活了活邻居中的Rho，从而将凋亡细胞挤出上皮。
Background: Simple epithelia encase developing embryos and organs. Although these epithelia consist of only one or two layers of cells, they must provide tight barriers for the tissues that they envelop. Apoptosis occurring within these simple epithelia could compromise this barrier. How, then, does an epithelium remove apoptotic cells without disrupting its function as a barrier?Results. We show that apoptotic cells are extruded from a simple epithelium by the concerted contraction of their neighbors. A ring of actin and myosin forms both within the apoptotic cell and in the cells surrounding it, and contraction of the ring formed in the live neighbors is required for apoptotic cell extrusion, as injection of a Rho GTPase inhibitor into these cells completely blocks extrusion. Addition of apoptotic MDCK cells to an intact monolayer induces the formation of actin cables in the cells contacted, suggesting that the signal to form the cable comes from the dying cell. The signal is produced very early in the apoptotic process, before procaspase activation, cell shrinkage, or phosphatidylserine exposure. Remarkably, electrical resistance studies show that epithelial barrier function is maintained, even when large numbers of dying cells are being extruded.Conclusions: We propose that apoptotic cell extrusion is important for the preservation of epithelial barrier function during cell death. Our results suggest that an early signal from the dying cell activates Rho in live neighbors to extrude the apoptotic cell out of the epithelium.