Desmosomal Junctions Govern Tissue Integrity and Actomyosin Contractility in Apoptotic Cell Extrusion
Desmosomal Junctions Govern Tissue Integrity and Actomyosin Contractility in Apoptotic Cell Extrusion
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DOI：
10.1016/j.cub.2020.01.002
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发表时间：
2020-02-24
期刊：
影响因子：
9.2
通讯作者：
Toyama, Yusuke
中科院分区：
文献类型：
--
作者：
Thomas, Minnah;Ladoux, Benoit;Toyama, Yusuke
在细胞凋亡或程序性细胞死亡过程中，死亡细胞可以通过死亡细胞与其邻近细胞之间的协调过程从组织中排出。细胞凋亡的挤出是由肌动球蛋白电缆的形成及其收缩和邻近细胞的片脂爬行驱动的[1-4]。在整个细胞挤出过程中，需要维持上皮细胞的机械耦合，以保持组织的动态平衡[1]。虽然人们对黏附连接(AJ)在细胞凋亡排泄中的调控已知很多[4-7]，但桥粒连接(DJ)在这一过程中的作用和动态仍然知之甚少。在这里，我们展示了DJ始终保持完好，并且对细胞挤出至关重要。即使在非死亡细胞之间形成新的DJ时，凋亡细胞与相邻细胞之间已存在的DJ仍然完好无损，这表明相邻细胞在凋亡细胞挤出的过程中存在两个DJ。我们进一步发现，在DJ附近形成了一条肌动球蛋白缆线，随后在其收缩过程中偏离了DJ。有趣的是，DJ的肌动球蛋白电缆线与DJ失去直线度的时间相吻合，这表明DJ的连接张力释放，DJ和肌动球蛋白的收缩能力之间存在机械耦合。桥粒蛋白的耗竭导致收缩功能缺陷，不能形成新生DJ，导致凋亡细胞排出失败。我们的研究提供了一个框架来解释桥粒如何在凋亡细胞挤出过程中在维持上皮片完整性方面发挥关键作用。
During apoptosis, or programmed cell death, a dead cell could be expelled from the tissue by coordinated processes between the dying cell and its neighbors. Apoptotic cell extrusion is driven by actomyosin cable formation and its contraction and lamellipodial crawling of the neighboring cells [1-4]. Throughout cell extrusion, the mechanical coupling of epithelia needs to be maintained in order to preserve tissue homeostasis [1]. Although much is known about the regulation of adherens junctions (AJs) in apoptotic cell extrusion [4-7], the role and dynamics of desmosomal junctions (DJs) during this process remain poorly understood. Here, we show that DJs stay intact throughout and are crucial for cell extrusion. Pre-existing DJs between the apoptotic cell and neighboring cells remain intact, even during the formation of de novo DJs between non-dying cells, suggesting the neighboring cells possess two DJs in the middle of apoptotic cell extrusion. We further found that an actomyosin cable formed in the vicinity of DJs upon apoptosis and subsequently deviated from DJs during its constriction. Interestingly, the departure of the actomyosin cable from DJs coincided with the timing when DJs lost their straightness, suggesting a release of junctional tension at DJs and a mechanical coupling between DJs and actomyosin contractility. The depletion of desmoplakin resulted in defective contractility and an inability to form de novo DJs, leading to a failure of apoptotic cell extrusion. Our study provides a framework to explain how desmosomes play pivotal roles in maintaining epithelial sheet integrity during apoptotic cell extrusion.