MRCKα is activated by caspase cleavage to assemble an apical actin ring for epithelial cell extrusion.
MRCKα is activated by caspase cleavage to assemble an apical actin ring for epithelial cell extrusion.
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DOI：
10.1083/jcb.201703044
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发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Primo L
中科院分区：
文献类型：
--
作者：
Gagliardi PA;Somale D;Puliafito A;Chiaverina G;di Blasio L;Oneto M;Bianchini P;Bussolino F;Primo L
凋亡细胞挤出对于维持上皮功能是至关重要的，并且依赖于由肌动球蛋白细胞骨架介导的复杂形态学事件。Gagliardi等人表明，半胱天冬酶介导的MRCKα切割触发了顶端肌动蛋白环的组装和凋亡上皮的挤出。从上皮组织中挤出凋亡细胞需要凋亡细胞及其邻居的协调的形态学重排。然而，凋亡级联反应和导致挤出的事件之间的联系尚未完全了解。在这里，我们的特点是凋亡挤压顶端肌动蛋白环（EAAR），组装在凋亡细胞和驱动上皮细胞的挤压。胱天蛋白酶介导的强直性肌营养不良激酶相关的CDC 42结合激酶-α（MRCKα）的切割触发了一条信号通路，该通路导致EAAR的组装，EAAR拉动肌动蛋白束，导致细胞体的压缩和去除。我们提供了一个详细的画像EAAR包括F-肌动蛋白流动，肌球蛋白收缩的贡献，和肌动蛋白聚合在束的终端时，表达的产物MRCKα切割。这些结果增加了我们对控制上皮细胞挤出过程的机制的理解，通过建立细胞凋亡的触发事件、MRCKα的激活及其对肌动球蛋白细胞骨架重排动力学的后续影响之间的因果关系。
Apoptotic cell extrusion is critical for the maintenance of epithelial functionality and relies on complex morphological events mediated by the actomyosin cytoskeleton. Gagliardi et al. show that caspase-mediated cleavage of MRCKα triggers the assembly of an apical actin ring and apoptotic epithelial extrusion. Extrusion of apoptotic cells from epithelial tissues requires orchestrated morphological rearrangements of the apoptotic cell and its neighbors. However, the connections between the apoptotic cascade and events leading to extrusion are not fully understood. Here, we characterize an apoptotic extrusion apical actin ring (EAAR) that is assembled within the apoptotic cell and drives epithelial extrusion. Caspase-mediated cleavage of myotonic dystrophy kinase–related CDC42-binding kinase-α (MRCKα) triggers a signaling pathway that leads to the assembly of EAAR that pulls actin bundles, resulting in the compaction and removal of the cell body. We provide a detailed portrait of the EAAR including F-actin flow, the contribution of myosin contraction, and actin polymerization at bundles' terminals when the product of MRCKα cleavage is expressed. These results add to our understanding of the mechanisms controlling the process of epithelial extrusion by establishing a causal relationship between the triggering events of apoptosis, the activation of MRCKα, and its subsequent effects on the dynamics of actomyosin cytoskeleton rearrangement.
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