Centre for Cancer Biology, University of South Australia & SA Pathology, GPO Box 2471, Adelaide, SA 5001, Australia.
Centre for Cancer Biology, University of South Australia & SA Pathology, GPO Box 2471, Adelaide, SA 5001, Australia.
Biochem Pharmacol. 2019 Apr;162:3-13. doi: 10.1016/j.bcp.2018.10.027. Epub 2018 Oct 26.
Autophagy-dependent cell death is a distinct mode of regulated cell death required in a context specific manner. One of the best validated genetic models of autophagy-dependent cell death is the removal of the Drosophila larval midgut during larval-pupal transition. We have previously shown that down-regulation of growth signaling is essential for autophagy induction and larval midgut degradation. Sustained growth signaling through Ras and PI3K blocks autophagy and consequently inhibits midgut degradation. In addition, the morphogen Dpp plays an important role in regulating the correct timing of midgut degradation. Here we explore the potential roles of Hh and Wg signaling in autophagy-dependent midgut cell death. We demonstrate that Hh and Wg signaling are not involved in the regulation of autophagy-dependent cell death. However, surprisingly we found that one key component of these pathways, the Drosophila Glycogen Synthase Kinase 3, Shaggy (Sgg), may regulate midgut cell size independent of Hh and Wg signaling.
自噬依赖性细胞死亡是一种特定的细胞程序性死亡方式，在特定的背景下具有重要的生物学意义。自噬依赖性细胞死亡的一个经过充分验证的遗传模型是在果蝇幼虫到蛹的转变过程中，幼虫肠道的去除。我们之前的研究表明，生长信号的下调对于自噬的诱导和幼虫肠道的降解是必需的。通过 Ras 和 PI3K 持续的生长信号会阻止自噬，从而抑制肠道降解。此外，形态发生素 Dpp 在调节肠道降解的正确时间方面发挥着重要作用。在这里，我们探讨了 Hh 和 Wg 信号通路在自噬依赖性肠道细胞死亡中的潜在作用。我们证明 Hh 和 Wg 信号通路不参与自噬依赖性细胞死亡的调节。然而，令人惊讶的是，我们发现这些信号通路的一个关键组成部分，果蝇糖原合成激酶 3（GSK3），Shaggy（Sgg），可能独立于 Hh 和 Wg 信号通路调节肠道细胞大小。
