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標題: | 探討醣解酶在細胞缺乏葡萄糖時內吞作用的調控機制 The role of glycolytic enzymes in regulating endocytosis upon glucose starvation |
作者: | 姚舒云 Shu-Yun Yao |
指導教授: | 許家維 Jia-Wei Hsu |
關鍵字: | 醣解酵素,內吞運送系統,內吞作用,葡萄糖缺乏,蛋白質兼職功能, glycolytic enzyme,endocytic transport,endocytosis,glucose starvation,protein moonlighting function, |
出版年 : | 2023 |
學位: | 碩士 |
摘要: | 葡萄糖缺乏對於細胞存活是一個重要的挑戰,會影響細胞內代謝途徑。雖然在葡萄糖缺乏時細胞的能量平衡機制已經被廣泛研究,但其他機制則了解較少。我們進行了體內運輸篩選實驗,包括運鐵蛋白受體(TfR)、表皮生長因子受體(EGFR)的內吞作用、以及葡萄糖聚醣(dextran)的液相內吞作用(基於顯微鏡觀察並定量分析的方法)。在本篇研究中,我們發現醣解酶丙酮酸激酶 M2(PKM2)和磷酸甘油酸激酶 1(PGK1)參與在葡萄糖缺乏之下調控蛋白質內吞運送過程。抑制 PKM2 和PGK1 進一步促進了 TfR 的內吞作用。進一步的研究表明,在葡萄糖缺乏時,內吞的抑制作用與這些酶的催化活性無關。這些發現表明醣解酶在葡萄糖缺乏時抑制蛋白質的內吞作用,這揭示了醣解酵素的新功能,作為蛋白質運送的調控因子。 Glucose starvation has been a fundamental challenge for cell survival to influence intracellular metabolic pathways. Whereas the effect of energy balance upon glucose starvation has been extensively characterized, other mechanisms are less discovered. We conducted in vivo transport screening assays, including endocytosis of transferrin receptor (TfR), epidermal growth factor receptor (EGFR), and fluid-phase endocytosis of dextran, a quantitative microscopy-based approach. Here we identify glycolytic enzymes, pyruvate kinase M2 (PKM2) and phosphoglycerate kinase 1 (PGK1), both participate in regulating endocytic protein trafficking upon glucose starvation. Inhibition of PKM2 and PGK1 further enhances the endocytosis of the TfR. Further characterization suggests that the endocytic inhibition during glucose starvation is independent of their catalytic activities. These findings suggest the inhibitory role of glycolytic enzymes for the endocytic protein transport upon glucose starvation which underlies a critical mechanism of the moonlighting function of glycolytic enzyme as the regulator for protein transport. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88954 |
DOI: | 10.6342/NTU202303247 |
全文授權: | 未授權 |
顯示於系所單位: | 生化科學研究所 |
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