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標題: | 探討 Stx17 蛋白在細胞自噬作用之分子機轉 Molecular regulation of Stx17 during autophagy |
作者: | Yi-Hsun Chung 鐘怡洵 |
指導教授: | 陳光超 |
關鍵字: | 細胞自噬,Syntaxin17,磷酸化,可溶性 NSF 附著蛋白受體 (SNAREs),PTP1B,TC48, Autophagy,Syntaxin17,Phosphorylation,SNARE proteins,PTP1B,TC48, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | 當細胞面對營養壓力或發育時,會進行一個自我消化的過程稱為細胞自噬 (Autophagy),此過程對平衡細胞能量來源來說十分重要。當引發細胞自噬時,細胞內的物質將受到雙層膜構造包覆,此構造稱為細胞自噬體。而細胞自噬體最終會和溶酶體融合,並將包覆的物質分解並回收。Syntaxin17 (STX17)為一個可溶性NSF 附著蛋白受體 (SNARE),在細胞自噬的引發與細胞自噬體的成熟中扮演了重要的角色;然而,STX17的功能是否會受到酪胺酸磷酸化調控的相關機制尚未釐清。
根據我們的數據顯示,在飢餓條件下STX17會受到酪胺酸磷酸化。STX17 序列中,有三個酪胺酸具有物種間保守性質,根據點突變分析顯示,STX17主要受到磷酸化的位置坐落於面向細胞質液面的區域。深入研究後發現,當此位置的酪胺酸突變為苯丙胺酸時會導致細胞自噬缺陷。 我們更進一步確認STX17的磷酸酶和激酶,分別為TC48,PTP1B和Src。之後,我們更好奇於磷酸化的STX17 如何參與在細胞自噬中;而數據顯示,STX17酪胺酸突變會參與調控SNARE複合體的組成。總結來說,我們提出Src會磷酸化STX17;並且,在飢餓條件下由TC48或PTP1B為STX17進行去磷酸化。除此之外,STX17的酪胺酸磷酸化,可能在SNARE複合體的組成中扮演一個重要的角色。 Autophagy is a self-digestive process that is important in balancing sources of energy at critical times during development and in response to nutrient stress. Upon autophagy induction, cytoplasmic constituents are engulfed within double-membraned vesicles known as an autophagosomes which eventually fuse with lysosomes and the contents are degraded and recycled. Although syntaxin17 (STX17), an autophagic SNARE, plays a vital role in autophagy induction and autophagosome maturation, little is known about whether tyrosine phosphorylation is implicated in the function of STX17. Our recent data showed that Stx17 is tyrosine phosphorylated under starvation. There are three conserved tyrosine residues in STX17, mutational analysis showed one tyrosine residue in the cytoplasmic domain of STX17 as the major site of phosphorylation. We further found that tyrosine mutation of STX17 results in autophagic defects. TC48 and PTP1B were identified as the phosphatase of STX17, moreover, Src was identified as the kinase of STX17. We were curious about the mechanism of phosphorylation of STX17 in the autophagy. Our data suggested that STX17 mutants regulate SNARE complex assembly. Taken together, we propose that Src phosphorylates Syntaxin17. Furthermore, the dephosphorylation of Syntaxin17 during starvation requires TC48 and PTP1B. In addition, we suggest that tyrosine phosphorylation of Syntaxin 17 is likely to have a role in regulating the assembly of the SNARE complex. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68555 |
DOI: | 10.6342/NTU201704030 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科學研究所 |
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