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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 李芳仁(Fang-Jen S. Lee) | |
dc.contributor.author | Pei-Hua Tang | en |
dc.contributor.author | 湯佩樺 | zh_TW |
dc.date.accessioned | 2021-06-08T06:12:40Z | - |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-04 | |
dc.identifier.citation | Achstetter, T., Franzusoff, A., Field, C. and Schekman, R.(1988). SEC7 encodes an unusual, high molecular weight protein required for membrane traffic from the yeast Golgi apparatus. J Biol Chem 263, 11711–7.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25419 | - |
dc.description.abstract | 腺嘌呤核甘二磷酸核醣化因子(ADP-ribosylation factors,ARFs)在真核細胞的蛋白質運輸及細胞骨架的重組中扮演得很重要的角色。在酵母菌的研究當中已經知道第三腺嘌呤核甘二磷酸核醣化相似因子(Arl3p)會募集第一腺嘌呤核甘二磷酸核醣化相似因子(Arl1p)進而調控細胞中高基氏體(Golgi apparatus)的結構及功能。我們實驗室近來研究發現一種腺嘌呤核甘二磷酸核醣化因子(ARF)的鳥糞嘌呤核苷酸交換因子Syt1p會幫助Arl1p的活化並促進募集下游Imh1p到高基氏體上。過去的研究已經知道Syt1是磷酸化蛋白且發現了許多被磷酸化所調控的胺基酸位置。我們的研究更進一步確認Syt1確實可以被磷酸化所修飾,而研究中也發現Syt1鳥糞嘌呤核苷酸交換因子的活性可以被磷酸化所調控。在本篇研究中我們將更進一步探討磷酸化對Syt1的影響以及其修飾對於鳥糞嘌呤核苷酸交換因子的活性如何調控Arl1p活化。 | zh_TW |
dc.description.abstract | ARF-like (ARL) proteins belong to the ARF family, which regulate several vesicular trafficking pathways as well as cytoskeletal organization. In Saccharomyces cerevisiae, Arl3p recruits Arl1p GTPase to regulate Golgi function and structure. Our lab recently reported that an ARF-GEF Syt1p promotes Arl1p activation to recruit Imh1p to the Golgi. Syt1p is a phosphoprotein which contains multiple phosphorylation modifications according to previous finding. Our current data also confirmed that Syt1p was modifid by multiple phosphorylation modification and its GEF activity can be regulated by phosphorylation. In this study, we further analysis the phosphorylation in ARF-GEF Syt1p and characterize the role on Arl1p activation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T06:12:40Z (GMT). No. of bitstreams: 1 ntu-100-R98448004-1.pdf: 3718233 bytes, checksum: 1b90b0177a8af2c433bdddda9cc21a8a (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 中文摘要 -------------------------------------------------------------------------------------- Ⅴ
Abstract --------------------------------------------------------------------------------------- Ⅵ Abbreviation---------------------------------------------------------------------------------- Ⅶ Introduction----------------------------------------------------------------------------------- 1 ADP-ribosylation factor (ARFs) --------------------------------------------------------- 1 Guanine nucleotide exchange factors (GEFs) ----------------------------------------- 3 Arf-like proteins (ARLs )----------------------------------------------------------------- 6 Arl3p-Syt1p-Arl1p signaling pathway -------------------------------------------------- 8 Unfolded protein response (UPR) ------------------------------------------------------- 10 ER stress and trafficking------------------------------------------------------------------- 12 Syt1p phosphorylation is important for regulating the GEF activity of Syt1p and Arl1p activation----------------------------------------------------------------------------- 13 Materials and Methods--------------------------------------------------------------------- 16 Strains and Media-------------------------------------------------------------------------- 16 Plasmids and Strain Construction-------------------------------------------------------- 16 Polymerase Chain Reaction--------------------------------------------------------------- 18 Yeast cells extracts preparation and Western blotting--------------------------------- 19 In vivo pull-down assay-------------------------------------------------------------------- 21 Indirected Immuno fluorescence Staining---------------------------------------------- 24 Microscopy---------------------------------------------------------------------------------- 26 Yeast two hybrid screening---------------------------------------------------------------- 26 UPR stress treatment----------------------------------------------------------------------- 27 Results --------------------------------------------------------------------------------------- 29 Ire1p affect the activation of Arl1p to Golgi apparatus ------------------------------- 29 Ire1p affect Arl1p activation through the regulation of Syt1p phosphorylation--- 29 Arl1p activation could regulate through Ire1p-Hac1p pathway---------------------- 30 Phosphorylation at SerS416 of Styt1p would enhance the interaction between the Syt1p and GDP bound form Arl1p--------------------------------------------------------32 Cells lost ARL3, ARL1, SYT1 or IMH1 are sensitive to tunicamycin---------------------------------------------------------------------------------34 UPR stress could promote Golgi targeting of Imh1p --------------------------------- 35 Activation UPR stress or a mimetic phosphorylation mutant Syt1S416D could suppress ypt6 temperature-sensitive growth defect phenotype----------------------- 36 Searching for the putative kinase of Syt1p---------------------------------------------- 38 Discussion ---------------------------------------------------------------------------------- 41 Tables Table 1. Yeast strains used in this study------------------------------------------------ 47 Table 2. Primers used in this study------------------------------------------------------- 49 Table 3. Antibodies used in this study --------------------------------------------------50 Figures Figure 1. Imh1p location is diffusely distribution in ire1Δ cells------------ 51 Figure 2. Ire1p affect Imh1p Golgi location through Arl1p activation------- 52 Figure 3. Arl3p and Arf1p form Golgi-like punctuate in cell lacking Ire1p- 53 Figure 4. Ire1p affect Arl1p activation through the regulation of Syt1p Ser 416 phosphorylation----------------------------------------------------- 54 Figure 5. Mimetic phosphorylation mutant Syt1S416D could restore Arl1p and Imh1p location in cells lacking Ire1p----------------------------- 55 Figure 6. Kinase and RNase activities are required to rescue Imh1p location in ire1Δ cells-------------------------------------------------- 56 Figure 7. Kinase and RNase activities are required to restore Arl1p location in ire1 arl1Δ cells-------------------------------------------- 58 Figure 8. Imh1p is cytosolic distribution in lack of Hac1p, which is the downstream transcription factor of Ire1p----------------------------- 59 Figure 9. Constitutive active Hac1p could restore Imh1p location and Tunicamycin-sensitivity in ire1Δ cells------------------------------ 61 Figure 10. Constitutive active Hac1p could restore Imh1p location in ire1Δ but not arl3Δ, syt1Δor arl1Δcells----------------------------------- 62 Figure 11. Mimetic phosphorylation mutant Syt1S416D also could restore Imh1p location in hac1Δ strains-------------------------------------- 63 Figure 12. Ire1p affect the interaction of Syt1-GEF and Arl1T32N presumably through Syt1 Ser416 phosphrylation------------------- 64 Figure 13. arl3Δ, arl1Δ, syt1Δand imh1Δstrains are sensitive to tunicamycin -------------------------------------------------------------- 65 Figure 14. More mCherry-Imh1p were localized to Golgi while treatment with UPR-inducing agent----------------------------------------------- 66 Figure 15. Over-express Syt1S416D, Ire1p and constitutive active Hac1p could suppress temperature growth defect of ypt6Δ----------------- 67 Figure 16. The localization of mCherry-Imh1p in different kinase deletion strains --------------------------------------------------------------------- 68 Figure 17. Model of Ire1p-Hac1p regulate Arl1p activation and Imh1p recruitmen----------------------------------------------------------------- 69 Appendixes ------------------------------------------------------------------------------ 70 References ------------------------------------------------------------------------------ 72 | |
dc.language.iso | en | |
dc.title | 第一腺嘌呤核苷二磷酸核糖化相似因子之鳥糞嘌呤核苷酸交換因子的磷酸化可促進第一腺嘌呤核苷二磷酸核糖化相似因子活化之研究 | zh_TW |
dc.title | Characterize the role of Syt1p phosphorylation on Arl1p activation | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
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 | 第一腺嘌呤核苷,二磷酸核糖化相似因子,鳥糞嘌呤核苷,酸交換因子,磷酸化, | zh_TW |
dc.subject.keyword | Arl1p,Syt1p,phosphorylation, | en |
dc.relation.page | 78 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-08-04 | |
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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