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標題: | 第一腺嘌呤核苷二磷酸核醣化因子相似蛋白和高爾基體蛋白Imh1於酵母菌之功能性探討 Functional Characterization of small GTPase Arl1 and Golgin Protein Imh1 in Saccharomyces cerevisiae |
作者: | Yan-Ting Chen 陳彥廷 |
指導教授: | 李芳仁(Fang-Jen S. Lee) |
關鍵字: | 高爾基氏體,第一腺嘌呤核?二磷酸核糖化相似因子,高爾機體蛋白,內質網壓力,反向運輸, Arl1,Imh1,Sft2,UPR,ER stress,retrograde trafficking, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 腺嘌呤核苷二磷酸核糖化相似因子 (Arf-like protein, Arl) 在細胞體內扮演相當重要的角色,尤其是其調控囊泡運輸的功能。在釀酒酵母中,第一腺嘌呤核苷二磷酸核糖化相似因子 (Arl1) 負責在反式高爾基氏體網路 (trans-Golgi network) 上招募高爾基體蛋白Imh1,但是其詳細的功能並不是十分清楚。在我們先前的研究中,我們發現當細胞遭遇內質網壓力時,會促進Arl1以及其下游Imh1的活化。總而言之,我們仍不了解其作用的機轉以及活化的目的。在本篇研究中,我們發現當細胞遭遇內質網壓力時,被活化的Arl1以及Imh1會專一性的調控細胞中的反向運輸。有趣的是,Imh1的氨基端對於其功能是相當重要的,氨基端的突變會導致內質網壓力下反向運輸的缺陷。我們的研究指出,Imh1會透過招募一個被提出可能參與囊泡融合的蛋白質Sft2來達到其功能,雖然我們還需要繼續探討Sft2被Imh1所調控的機轉。與Imh1相同的是,Sft2的氨基端同樣也對於內質網壓力下的反向運輸非常重要。氨基端的突變也同樣會造成反向運輸無法運行。總結本篇,我們的研究意謂著細胞囊泡運輸系統在內質網壓力下的重要性。更多的是,我們提出了一個有趣的理論模式說明細胞中Imh1的功能並闡述了它的重要生理意義。 Arf-like proteins (Arls) are important regulators involved in a diversity of biological events, especially vesicle trafficking. In Saccharomyces cerevisiae, Arl1 acts to recruit a golgin protein Imh1 to the trans-Golgi network (TGN). However, besides the role of Imh1 as a high-copy suppressor of Ypt6, an important Rab protein mediating endosome-to-Golgi trafficking, less is known about it physiological significance. In previous studies (Hsu et al., 2016), they demonstrated that the Unfolded-Protein Response (UPR) augmented the activity of Arl1 and the subsequent Imh1 recruitment, but it remained to be elucidated on its specific functions under ER stress. Here, we showed that the UPR-activated Arl1 and Imh1 act to specifically maintain the endosome-to-Golgi trafficking when cell encounters ER stress. Moreover, this regulation does not simply depend on GARP complex recruitment, an important tethering complex, to affect retrograde trafficking. We found that the first five amino acids at Imh1 N-terminus is required for its function, as it contributes to the recruitment of Sft2, a tetra-spanning membrane protein involved in vesicle fusion. The N-terminus of Sft2 is responsible for facilitating the transport of Snc1 and Tlg1 and promoting retrograde trafficking. Together, our study is one of the first to demonstrate the physiological function of golgin Imh1 and elucidate the importance of the trafficking machinery in response to ER stress. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70482 |
DOI: | 10.6342/NTU201802833 |
全文授權: | 有償授權 |
顯示於系所單位: | 分子醫學研究所 |
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