Non-apoptotic function of Drosophila caspase activation in epithelial thorax closure and wound healing
Non-apoptotic function of Drosophila caspase activation in epithelial thorax closure and wound healing
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DOI：
10.1242/dev.169037
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发表时间：
2019-02-01
期刊：
影响因子：
4.6
通讯作者：
Miura, Masayuki
中科院分区：
文献类型：
--
作者：
Fujisawa, Yuya;Kosakamoto, Hina;Miura, Masayuki
非凋亡caspase激活涉及多个细胞事件。然而，可见的非凋亡caspase激活与其在生物体中的功能之间的联系尚未揭示。在这里，我们通过结合caspase 3激活的敏感指标和果蝇的活体成像分析，可视化了凋亡信号的亚致死激活。在蛹发育过程中胸腔闭合时，在边缘细胞中观察到caspase 3的特异性激活，无凋亡迹象。抑制caspase激活导致胸腔关闭速度增加，这表明非凋亡caspase活性在细胞运动中起作用。重要的是，在先前胸腔闭合的融合部位伤口闭合时也观察到半胱天冬酶3的亚致死激活。进一步的遗传分析表明，caspase Dronc的激活与活性氧的产生是耦合的。Dronc的激活还能调节肌球蛋白水平，延缓伤口愈合。我们的研究结果表明，在上皮关闭过程中，非凋亡性caspase激活在细胞迁移行为的微调中可能起作用。
Non-apoptotic caspase activation involves multiple cellular events. However, the link between visible non-apoptotic caspase activation and its function in living organisms has not yet been revealed. Here, we visualized sub-lethal activation of apoptotic signaling with the combination of a sensitive indicator for caspase 3 activation and in vivo live-imaging analysis of Drosophila. During thorax closure in pupal development, caspase 3 activation was specifically observed at the leading edge cells, with no signs of apoptosis. Inhibition of caspase activation led to an increase in thorax closing speed, which suggests a role of non-apoptotic caspase activity in cell motility. Importantly, sub-lethal activation of caspase 3 was also observed during wound closure at the fusion sites at which thorax closure had previously taken place. Further genetic analysis revealed that the activation of the initiator caspase Dronc is coupled with the generation of reactive oxygen species. The activation of Dronc also regulates myosin levels and delays wound healing. Our findings suggest a possible function for non-apoptotic caspase activation in the fine-tuning of cell migratory behavior during epithelial closure.