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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李芳仁(Fang-Jen S. Lee) | |
dc.contributor.author | Yi-Hsun Wang | en |
dc.contributor.author | 王奕勛 | zh_TW |
dc.date.accessioned | 2021-06-17T02:30:06Z | - |
dc.date.available | 2022-09-08 | |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-18 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68675 | - |
dc.description.abstract | 腺嘌呤核苷二磷酸核醣化相似因子 (ARF-like protein 1, ARL1) 屬於腺嘌呤核苷二磷酸核醣化因子家族的成員之一 (ADP-ribosylation factors, ARFs)。在真核生物中,這類蛋白被報導參與許多重要的細胞功能,包含調控囊泡運輸、影響細胞骨架的組裝以及維持細胞內的離子恆定等等,但是作用機制的細節仍不甚清楚。在酵母菌的研究當中,已知鳥糞嘌呤核苷酸交換因子 (Guanine nucleotide exchange factor) Syt1p 會催化 Arl1p 的活性並使其前往反式高基氏體網路 (trans-Golgi network)。活化態的 Arl1p 將吸引高基氏體蛋白 (Imh1p) 至反式高基氏體網路並作用於下游的囊泡運輸。在我們先前的發表成果中,我們發現內質網壓力 (ER stress) 的誘發將促使內質網上的磷酸化激酶 Ire1p 活性上升,Ire1p將透過 Syt1p 的第416號絲氨酸磷酸化轉譯後修飾進一步大量活化 Arl1p。此外,我們也證實這條路徑的啟動有助於細胞抵擋內質網壓力。而在本篇研究中,我們發現在細胞經歷內質網壓力的過程中, Hog1p 是另一個調控 Syt1p的磷酸化激酶。不同於 Ire1p 的是,Hog1p 作用於 Syt1p 的第297號絲氨酸磷酸化轉譯後修飾以活化 Arl1p。同時,我們亦發現不受壓力激活的 Hog1p 也可以調控 Arl1p 的活化,說明在壓力環境以及正常生理狀態下,Hog1p 皆扮演活化 Arl1p 的重要角色。總結本篇除了再次說明 Syt1p 的磷酸化轉譯後修飾對於 Arl1p 活化的重要性,我們亦提出 Hog1p 在正常生理狀態中所執行的新功能。 | zh_TW |
dc.description.abstract | ARF-like (ARL) proteins play important roles in regulating vesicular trafficking at the Golgi compartments, modulating cytoskeleton dynamics and maintaining ion homeostasis. In Saccharomyces cerevisiae, guanine-nucleotide exchange factor (GEF) Syt1p facilitates Arl1p activation to recruit golgin protein Imh1p to trans-Golgi network (TGN). Our previous findings have elucidated the induction of unfolded protein response (UPR) highly promotes activation of Arl1p and that ER-resident kinase Ire1p is responsible for the up-regulation through transcription alteration (Proc. Natl. Acad. Sci. U S A. 113:E1683-E1690). Moreover, the SYT1-ARL1-IMH1 signaling is required for ER stress resistance. In this study, we identified MAP kinase Hog1p as a new regulator of the ARL1 pathway for UPR. We found that MAP kinase controls Arl1p activation and non-stressed Hog1p mutant can rescue Imh1p Golgi localization in MAP kinase-deleted cells. We further showed that Hog1p might directly phosphorylate Syt1p at serine 297 to promote the activation of Arl1p, which performs a distinct route from Ire1p-mediated Syt1p phosphorylation at serine 416. Collectively, we demonstrate that Syt1p phosphorylation is regulated by multi-regulators, which is important for the activation and function of Arl1p under stress as well as normal growth conditions. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T02:30:06Z (GMT). No. of bitstreams: 1 ntu-106-R04448004-1.pdf: 6100281 bytes, checksum: dec6f9a37da95ad01b46929220689552 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 致謝 1
口試委員會審定書 2 Table of Contents 3 中文摘要 6 Abstract 7 Introduction 8 ADP-ribosylation factor (ARFs) and Arf-like proteins (ARLs) 8 Guanine nucleotide exchange factors (GEFs) 11 High Osmolarity Glycerol response kinase (HOG1) 12 Materials and Methods 16 Tables 25 Table 1. Yeast strains used in this study 25 Table 2. Plasmids used in this study 27 Table 3. Antibodies used in this study 29 Results 30 Hog1p alters Arl1p activation under non-stress or ER stress condition. 30 Canonical MAPK pathway is not required for Hog1p-regulated Arl1p signaling. 31 Hog1p catalytic activity but not stress-induced nuclear translocation is required for Arl1p cascade. 31 Hog1p modulates Syt1p-mediated Arl1p activation under normal growth conditions. 33 Hog1p phosphorylates Syt1p at serine 297 to activate Arl1p. 34 Hog1p plays a distinct role from Ire1p for Arl1p activation.. 37 Syt1p-mediated Arl1p activation is controlled by multi-regulators under stress as well as normal growth conditions.. 38 Discussion 39 The precise controls of GEFs on Arl1p activation in nature. 39 Uncovering non-stressed MAPK plays roles in normal physiology. 40 MAPK might devote to Golgi quality through the golgin recruitment. 43 Figures 45 Figure 1. Hog1p is required for the Golgi localization of Imh1p under ER stress and non-stress conditions. 45 Figure 2. Hog1p is required for the Golgi localization of Arl1p under ER stress and non-stress conditions. 46 Figure 3. Hog1p MAP kinase pathway does not alter Arl1p and Imh1p Golgi localization. 47 Figure 4. The catalytic activity of non-stressed Hog1p acts on Arl1p cascade. 49 Figure 5. Stress-induced phosphorylation and kinase activity are required for Hog1p nuclear translocation. 51 Figure 6. Hog1p is required the Golgi localization of Imh1p during non-stressed condition. 52 Figure 7. Hog1p is required for the activation of Arl1p during non-stressed condition. 54 Figure 8. Arl3p and Golgi markers were not affected by Hog1p. 56 Figure 9. Syt1p is required for the Hog1p-mediated Arl1p activation. 58 Figure 10. Hog1p interacts with Syt1p in the cells. 60 Figure 11. Hog1p contributes to the phosphorylation of the serine 297-contained Syt1p phosphor-peptides. 61 Figure 12. Hog1p contributes to the phosphorylation of the MAPK substrate motif in Syt1p at serine297 63 Figure 13. The phosphorylation of Syt1p serine 297 is required for the Golgi localization of Arl1p and mCherry-Imh1p. 64 Figure 14. The phosphorylation syt1p at serine 297 is required for the interaction to Arl1p. 65 Figure 15. Hog1p phosphorylates Syt1pS297 to promote the Arl1p pathway. 66 Figure 16. Hog1p undergoes a distinct route from the Ire1p-mediated Arl1p activation. 67 Figure 17. Highly raising the Hog1p-mideated Syt1p phosphorylation overcomes the defect of Arl1p pathway in IRE1 knockout cells. 68 Figure 18. A working model demonstrates the activation of Arl1p pathway during ER stress and non-stress conditions. 69 Supplements 70 Supplement 1. Glycerol synthesis genes are required for the Golgi localization of Imh1p. 70 Supplement 2. Arl3p is not affected by Glycerol synthesis genes. 71 Supplement 3. Golgi markers except Sft2p are not affected by Glycerol synthesis genes. 72 Supplement 4. Phosphor-mimetic Syt1p could not suppress the mislocalization of Imh1p in glycerol synthesis-defective cells. 73 Supplement 5. Overexpression of glycerol synthesis proteins could not suppressed the defect of Imh1p localization in HOG1 knockout cells. 74 Supplement 6. Glycerol treatment is sufficient to rescue the Golgi localization of Imh1p in glycerol synthesis-defective cells. 75 Supplement 7. The constitutively active mutation of Arl1p could overcome the defect of Golgi localization in glycerol synthesis-defective cells. 76 Supplement 8. Glycerol modulates the subdomain of Golgi membrane to affect the Arl1p pathway in the cells. 77 References 78 | |
dc.language.iso | zh-TW | |
dc.title | 高滲透壓甘油反應磷酸化激酶調控鳥糞嘌呤核苷酸交換因子以活化第一腺嘌呤核苷二磷酸核醣化相似因子之探討 | zh_TW |
dc.title | Characterization of Hog1p protein kinase in regulating Syt1p-mediated Arl1p activation | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳瑞華(Ruey-Hwa Chen),鄧述諄(Shu-Chun Teng),王昭雯(Chao-Wen Wang) | |
dc.subject.keyword | 高基氏體,鳥糞嘌呤核?酸交換因子,腺嘌呤核?二磷酸核醣化相似因子,高滲透壓甘油反應磷酸化激?, | zh_TW |
dc.subject.keyword | trans-Golgi network,GEFs,Arls,Hog1, | en |
dc.relation.page | 88 | |
dc.identifier.doi | 10.6342/NTU201703994 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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