EGFR 信号刺激自噬以调节果蝇睾丸中的干细胞维持和脂质稳态。
EGFR Signaling Stimulates Autophagy to Regulate Stem Cell Maintenance and Lipid Homeostasis in the Drosophila Testis.
机构信息
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Cell Rep. 2020 Jan 28;30(4):1101-1116.e5. doi: 10.1016/j.celrep.2019.12.086.
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.
虽然自噬通常在细胞应激时上调，但它也可以在稳态条件下作为质量控制机制或响应发育信号而被利用。在这里，我们报告自噬对于果蝇睾丸中体腔干细胞（CySCs）的维持是必需的。通过耗尽自噬相关（Atg）基因在 CySCs 和早期囊泡细胞（CCs）中破坏自噬，减少了早期 CC 的数量并影响了 CC 的功能，类似于表皮生长因子受体（EGFR）信号的减少。事实上，我们的数据表明，EGFR 作用于刺激自噬以维持早期 CC 功能，而雷帕霉素靶蛋白（TOR）在分化的 CCs 中负调控自噬。最后，我们表明，EGFR 介导的自噬刺激调节 CySCs 和 CCs 中的脂质水平。这些结果表明，自噬在通过整合来自 EGFR 和 TOR 信号通路的线索来控制脂质代谢，从而调节体腔干细胞行为和组织动态平衡方面发挥着关键作用。
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