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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許家維 | zh_TW |
| dc.contributor.advisor | Jia-Wei Hsu | en |
| dc.contributor.author | 姚舒云 | zh_TW |
| dc.contributor.author | Shu-Yun Yao | en |
| dc.date.accessioned | 2023-08-16T16:30:55Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-08-16 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-07 | - |
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Front Oncol, 10, 159. https://doi.org/10.3389/fonc.2020.00159 Zala, D., Hinckelmann, M. V., Yu, H., Lyra da Cunha, M. M., Liot, G., Cordelieres, F. P., Marco, S., & Saudou, F. (2013). Vesicular glycolysis provides on-board energy for fast axonal transport. Cell, 152(3), 479-491. https://doi.org/10.1016/j.cell.2012.12.029 Cooper, G. M. (2000). The Cell: A Molecular Approach. (2nd edition.). Sinauer Associates. https://www.ncbi.nlm.nih.gov/books/NBK9831/ | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88954 | - |
| dc.description.abstract | 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。 | zh_TW |
| dc.description.abstract | 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. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-08-16T16:30:55Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-08-16T16:30:55Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
摘要 ii Abstract iii Table of Contents iv List of Figures viii Chapter 1 Introduction 1 1.1 Literature Review 1 1.1.1 Clathrin-mediated endocytosis (CME) 1 1.1.2 Phosphoglycerate kinase 1 (PGK1) 3 1.1.3 Pyruvate kinase M2 (PKM2) 4 1.1.4 Glucose starvation and endocytic transport 6 1.2 Study Background 7 Chapter 2 Material and Method 9 2.1 Chemicals, proteins, and antibodies 9 2.2 Cell culture and glucose starvation treatment 10 2.3 Sequences for siRNA. 11 2.4 Construction of plasmids 11 2.5 Site-directed mutagenesis 12 2.6 Transfection 13 2.6.1 siRNA knockdown 13 2.6.2 Transfection 14 2.7 SDS-PAGE and Western blotting 15 2.7.1 SDS-PAGE 15 2.7.2 Western blotting 15 2.8 In vivo protein transport assay 16 2.8.1 The fluid-phase uptake of dextran, 16 2.8.2 The endocytosis of EGFR 17 2.8.3 The endocytosis of TfR 17 2.8.4 Protein transport under glucose starvation 17 2.9 Immunofluorescence 18 2.10 Confocal microscopy 18 2.11 Image analysis 19 2.11.1 Colocalization 19 2.11.2 Early endosome number and surface binding Tf 19 2.11.3 Internalized Tf 19 2.12 Subcellular fractionation 20 2.13 Statistical analysis 20 Chapter 3 Experimental Result 22 3.1 Knocking down PGK1 and PKM2 does not affect TfR, EGFR endocytosis, and macropinocytosis. 22 3.2 Glucose starvation promotes endocytosis of TfR, EGFR, and macropinocytosis. 23 3.3 Knocking down PGK1 and PKM2 further promotes TfR endocytosis upon glucose starvation. 25 3.4 Further characterizing synergistic regulation in endocytosis. 27 3.5 Further analyzing intracellular localization of PGK1 and PKM2. 28 Chapter 4 Discussion 30 4.1 Knocking down PGK1 and PKM2 does not affect endocytosis under normal physiological conditions. 30 4.2 Knocking down PGK1 and PKM2 promotes endocytosis upon glucose starvation. 30 Chapter 5 Figure 32 References 69 | - |
| dc.language.iso | en | - |
| dc.subject | 蛋白質兼職功能 | zh_TW |
| dc.subject | 醣解酵素 | zh_TW |
| dc.subject | 內吞運送系統 | zh_TW |
| dc.subject | 內吞作用 | zh_TW |
| dc.subject | 葡萄糖缺乏 | zh_TW |
| dc.subject | endocytic transport | en |
| dc.subject | glycolytic enzyme | en |
| dc.subject | protein moonlighting function | en |
| dc.subject | glucose starvation | en |
| dc.subject | endocytosis | en |
| dc.title | 探討醣解酶在細胞缺乏葡萄糖時內吞作用的調控機制 | zh_TW |
| dc.title | The role of glycolytic enzymes in regulating endocytosis upon glucose starvation | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 劉雅雯;姚季光 | zh_TW |
| dc.contributor.oralexamcommittee | Ya-Wen Liu;Chi-Kuang Yao | en |
| dc.subject.keyword | 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, | zh_TW |
| dc.subject.keyword | glycolytic enzyme,endocytic transport,endocytosis,glucose starvation,protein moonlighting function, | en |
| dc.relation.page | 73 | - |
| dc.identifier.doi | 10.6342/NTU202303247 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-08-09 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科學研究所 | - |
| 顯示於系所單位： | 生化科學研究所 | |
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