The role of the effector caspases drICE and dcp-1 for cell death and corpse clearance in the developing optic lobe in Drosophila

The role of the effector caspases drICE and dcp-1 for cell death and corpse clearance in the developing optic lobe in Drosophila
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DOI:
10.1016/j.ydbio.2015.05.013
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发表时间:
2015-08-15
影响因子:
2.7
通讯作者:
Tsujimura, Hidenobu
Tsujimura, Hidenobu
中科院分区:
生物学3区
文献类型:
--
作者:
Akagawa, Hiromi;Hara, Yusuke;Tsujimura, Hidenobu

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在发育中的果蝇视叶中,细胞死亡通过凋亡发生,并以独特的死亡细胞簇的时空模式发生。我们分析了效应半胱天冬酶drICE和dcp-1在视叶细胞死亡和随后的尸体清除突变体的作用。许多簇中的神经元需要drICE或dcp-1,每一个都足够了。这表明drICE和dcp-1在细胞死亡中起冗余作用。然而,在一些集群中的垂死的神经元严格需要drICE,而不是dcp-1,但需要drICE和dcp-1时,drICE活性降低通过亚型突变。此外,对突变体的分析表明效应半胱天冬酶在尸体清除中起重要作用。在无效和亚纯型drICE突变体中,观察到比野生型更多的TUNEL阳性细胞,并且许多TUNEL阳性细胞保持到后期阶段。Lysotracker染色显示这些突变体在尸体清除方面存在缺陷。所有的结果表明,drICE在激活死亡细胞的尸体清除中起着重要的作用,并且效应半胱天冬酶的额外功能是激活尸体清除以及进行细胞死亡所必需的。(C)2015 Elsevier Inc. All rights reserved.
In the developing Drosophila optic lobe, cell death occurs via apoptosis and in a distinctive spatiotemporal pattern of dying cell clusters. We analyzed the role of effector caspases drICE and dcp-1 in optic lobe cell death and subsequent corpse clearance using mutants. Neurons in many clusters required either drICE or dcp-1 and each one is sufficient. This suggests that drICE and dcp-1 function in cell death redundantly. However, dying neurons in a few clusters strictly required drICE but not dcp-1, but required drICE and dcp-1 when drICE activity was reduced via hypomorphic mutation. In addition, analysis of the mutants suggests an important role of effecter caspases in corpse clearance. In both null and hypomorphic drICE mutants, greater number of TUNEL-positive cells were observed than in wild type, and many TUNEL-positive cells remained until later stages. Lysotracker staining showed that there was a defect in corpse clearance in these mutants. All the results suggested that drICE plays an important role in activating corpse clearance in dying cells, and that an additional function of effector caspases is required for the activation of corpse clearance as well as that for carrying out cell death. (C) 2015 Elsevier Inc. All rights reserved.