鉴定葡萄糖-6-磷酸转运蛋白作为在自噬起始步骤中起关键调节作用的关键调节剂。
Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step.
机构信息
Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea; Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA.
出版信息
FEBS Lett. 2015 Jul 22;589(16):2100-9. doi: 10.1016/j.febslet.2015.05.018. Epub 2015 May 15.
Autophagy is a catabolic process involving autophagosome formation via lysosome. However, the initiation step of autophagy is largely unknown. We found an interaction between ULK1 and ATG9 in mammalian cells and utilized the interaction to identify novel regulators of autophagy upstream of ULK1. We established a cell-based screening assay employing bimolecular fluorescence complementation. By performing gain-of-function screening, we identified G6PT as an autophagy activator. G6PT enhanced the interaction between N-terminal Venus-tagged ULK1 and C-terminal Venus-tagged ATG9, and increased autophagic flux independent of its transport activity. G6PT negatively regulated mTORC1 activity, demonstrating that G6PT functions upstream of mTORC1 in stimulating autophagy.
自噬是一个涉及溶酶体的自噬体形成的分解代谢过程。然而，自噬的起始步骤在很大程度上是未知的。我们在哺乳动物细胞中发现了 ULK1 和 ATG9 之间的相互作用，并利用这种相互作用来鉴定 ULK1 上游的自噬新调节因子。我们建立了一种基于细胞的双分子荧光互补筛选测定法。通过进行功能获得筛选，我们鉴定出 G6PT 是一种自噬激活剂。G6PT 增强了 N 端 Venus 标记的 ULK1 和 C 端 Venus 标记的 ATG9 之间的相互作用，并增加了独立于其转运活性的自噬通量。G6PT 负调控 mTORC1 活性，表明 G6PT 在刺激自噬中作为 mTORC1 的上游因子发挥作用。
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