Caspases function in autophagic programmed cell death in Drosophila
Caspases function in autophagic programmed cell death in Drosophila
复制标题
DOI：
10.1242/dev.00933
复制
发表时间：
2004-01-01
期刊：
影响因子：
4.6
通讯作者：
Baehrecke, EH
中科院分区：
文献类型：
--
作者：
Martin, DN;Baehrecke, EH
细胞质成分的自我消化是自噬性程序性细胞死亡的标志。这种自动降解似乎与被吞噬细胞吞噬和消化的凋亡细胞中发生的情况不同。尽管人们对细胞凋亡了解很多，但对调节自噬细胞死亡的机制知之甚少。在这里，我们表明自噬性细胞死亡是通过果蝇唾液腺中半胱天冬酶的类固醇激活来调节的。唾液腺表现出一些与凋亡细胞相似的形态变化，包括细胞质破碎，但似乎在降解过程中不使用吞噬细胞。丝状肌动蛋白、α-微管蛋白、α-血影蛋白和核纤层蛋白的水平和定位发生变化先于唾液腺破坏，并且与活性 Caspase 3 和裂解形式的核纤层蛋白的水平增加相一致。防止唾液腺细胞死亡的类固醇调节基因 betaFTZ-F1、E93、BR-C 和 E74A 中的突变会改变丝状肌动蛋白、α-微管蛋白、α-血影蛋白、核纤层蛋白和活性 Caspase 3 的水平和定位。通过表达 caspase 抑制剂 p35 或启动子 caspase Dronc 的显性失活形式来抑制 caspase，足以抑制唾液腺细胞死亡，并阻止核纤层蛋白和α-微管蛋白的变化，但不阻止丝状肌动蛋白的重组。这些研究表明，垂死唾液腺的变化可能需要细胞骨架的某些方面。此外，半胱天冬酶不仅在细胞凋亡过程中使用，还在自噬性细胞死亡的调节中发挥作用。
Self-digestion of cytoplasmic components is the hallmark of autophagic programmed cell death. This auto-degradation appears to be distinct from what occurs in apoptotic cells that are engulfed and digested by phagocytes. Although much is known about apoptosis, far less is known about the mechanisms that regulate autophagic cell death. Here we show that autophagic cell death is regulated by steroid activation of caspases in Drosophila salivary glands. Salivary glands exhibit some morphological changes that are similar to apoptotic cells, including fragmentation of the cytoplasm, but do not appear to use phagocytes in their degradation. Changes in the levels and localization of filamentous Actin, alpha-Tubulin, a-Spectrin and nuclear Lamins precede salivary gland destruction, and coincide with increased levels of active Caspase 3 and a cleaved form of nuclear Lamin. Mutations in the steroid-regulated genes betaFTZ-F1, E93, BR-C and E74A that prevent salivary gland cell death possess altered levels and localization of filamentous Actin, alpha-Tubulin, alpha-Spectrin, nuclear Lamins and active Caspase 3. Inhibition of caspases, by expression of either the caspase inhibitor p35 or a dominant-negative form of the initiator caspase Dronc, is sufficient to inhibit salivary gland cell death, and prevent changes in nuclear Lamins and alpha-Tubulin, but not to prevent the reorganization of filamentous Actin. These studies suggest that aspects of the cytoskeleton may be required for changes in dying salivary glands. Furthermore, caspases are not only used during apoptosis, but also function in the regulation of autophagic cell death.