AP1蛋白和反面高尔基体在自噬体形成中的重要作用

发布时间：2018-06-27 13:37

本文选题：自噬体 + 膜泡运输　；参考：《浙江大学》2011年硕士论文

【摘要】：自噬是真核细胞中广泛存在的降解和再循环系统,与细胞及机体的多种生理和病理过程密切相关。尽管最近关于自噬在发育和病理情况下功能的研究取得了很大进展,但是关于自噬体的形成和自噬体膜的来源尚存在争议。本课题的研究表明阻断蛋白运输通路可以显著抑制自噬体的形成,后高尔基体膜泡运输在自噬体的形成过程中发挥重要作用。我们的研究发现,增加反面高尔基体至细胞膜的蛋白运输促进了自噬体的形成。在自噬发生早期阶段,自噬相关蛋白LC3结合到反面高尔基体膜的特定区域,随后从反面高尔基体膜上脱离形成LC3阳性囊泡。但是这些LC3阳性囊泡既不与反面高尔基体向细胞膜运输的分泌蛋白融合,也分离于反面高尔基体向内涵体的运输。饥饿和rapamycin处理诱导产生自噬时,网格蛋白的适配蛋白APl可以结合到自噬体上。我们还发现,阻碍AP1介导的网格蛋白小泡在反面高尔基体膜的形成而不是在细胞膜的形成会抑制自噬体的形成。我们的结果提示,反面高尔基体可以通过APl依赖LC3阳性囊泡的形式为自噬体形成提供膜来源,从而在自噬体形成中发挥重要作用。
[Abstract]:Autophagy is a widespread degradation and recirculation system in eukaryotic cells, which is closely related to many physiological and pathological processes of cells and organisms. Although recent advances have been made in the study of autophagy in developmental and pathological conditions, the formation of autophagy and the origin of autophagy membrane are still controversial. Our study showed that blocking the protein transport pathway can significantly inhibit the formation of autophagy, and the transport of Golgi vesicle plays an important role in the formation of autophagy. Our study found that increased transport of proteins from the reverse Golgi body to the cell membrane promotes autophagy formation. In the early stage of autophagy, autophagy associated protein LC3 was bound to a specific region of the reverse Golgi body membrane, and then separated from the reverse Golgi body membrane to form LC3 positive vesicles. However, these LC3 positive vesicles were not fused with secretory proteins transported from the opposite Golgi body to the cell membrane, but also separated from the transport of the reverse Golgi body to the inner body. When starvation and rapamycin treatment induce autophagy, aptamer APL of griddle protein can bind to autophagy. We also found that blocking AP1-mediated reticular vesicles in the formation of Golgi membrane on the opposite side rather than on the membrane inhibited the formation of autophagy. Our results suggest that the reverse Golgi body can provide membrane source for autophagy formation through APL dependent LC3 positive vesicles and thus play an important role in autophagy formation.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

【相似文献】