EGFR Signaling Stimulates Autophagy to Regulate Stem Cell Maintenance and Lipid Homeostasis in the Drosophila Testis
EGFR Signaling Stimulates Autophagy to Regulate Stem Cell Maintenance and Lipid Homeostasis in the Drosophila Testis
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DOI：
10.1016/j.celrep.2019.12.086
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发表时间：
2020-01-28
期刊：
影响因子：
8.8
通讯作者：
Jones, D. Leanne
中科院分区：
文献类型：
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作者：
Demarco, Rafael Senos;Uyemura, Bradley S.;Jones, D. Leanne
虽然通常在细胞应激时上调，但自噬也可以在稳态条件下用作质量控制机制或响应于发育线索。在这里，我们报告说，自噬所需的维持体细胞囊肿干细胞（CySC）在果蝇睾丸。通过耗尽自噬相关（Atg）基因破坏CySC和早期囊肿细胞（CC）中的自噬，减少早期CC数量并影响CC功能，类似于表皮生长因子受体（EGFR）信号转导的减少。事实上，我们的数据表明，表皮生长因子受体的行为，以刺激自噬，以保持早期CC功能，而雷帕霉素（TOR）的目标，负调控分化的CC自噬。最后，我们发现EGFR介导的自噬刺激调节CySC和CC中的脂质水平。这些结果证明了自噬在调节体干细胞行为和组织稳态中的关键作用，其通过整合来自EGFR和TOR信号通路的线索来控制脂质代谢。
Although typically upregulated upon cellular stress, autophagy can also be utilized under homeostatic conditions as a quality control mechanism or in response to developmental cues. Here, we report that autophagy is required for the maintenance of somatic cyst stem cells (CySCs) in the Drosophila testis. Disruption of autophagy in CySCs and early cyst cells (CCs) by the depletion of autophagy-related (Atg) genes reduced early CC numbers and affected CC function, resembling decreased epidermal growth factor receptor (EGFR) signaling. Indeed, our data indicate that EGFR acts to stimulate autophagy to preserve early CC function, whereas target of rapamycin (TOR) negatively regulates autophagy in the differentiating CCs. Finally, we show that the EGFR-mediated stimulation of autophagy regulates lipid levels in CySCs and CCs. These results demonstrate a key role for autophagy in regulating somatic stem cell behavior and tissue homeostasis by integrating cues from both the EGFR and TOR signaling pathways to control lipid metabolism.