跳到主要內容

臺灣博碩士論文加值系統

(44.210.99.209) 您好!臺灣時間:2024/04/15 18:13
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:鐘怡洵
研究生(外文):Yi-Hsun Chung
論文名稱:探討 Stx17 蛋白在細胞自噬作用之分子機轉
論文名稱(外文):Molecular regulation of Stx17 during autophagy
指導教授:陳光超陳光超引用關係
口試日期:2017-07-25
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:55
中文關鍵詞:細胞自噬Syntaxin17磷酸化可溶性 NSF 附著蛋白受體 (SNAREs)PTP1BTC48
外文關鍵詞:AutophagySyntaxin17PhosphorylationSNARE proteinsPTP1BTC48
相關次數:
  • 被引用被引用:0
  • 點閱點閱:190
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
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.
Contents
口試委員會審定書 I
中文摘要 II
Abstract III
Contents IV
Introduction 1
Autophagy 1
Autophagy overview 1
(1) Induction 2
(2) Autophagosome formation 3
(3) Degradation 5
SNARE proteins 6
SNARE proteins overview 6
Phosphorylation regulates fusion event 10
Connection between SNARE and autophagy 11
Material and Methods 18
Cell culture, transfection and treatments 19
Generation of knockdown cell line 20
Plasmids 21
Immunoprecipitation, sample preparation, and western blotting 21
Results 24
Syntaxin17 is tyrosine phosphorylated during starvation 24
Tyrosine phosphorylation of Syntaxin 17 is required for autophagy 25
Syntaxin17 interacts with PTP1B and TC48 25
Syntaxin17 is a substrate of PTP1B and TC48 26
Src is the kinase of Syntaxin17 27
The tyrosine phosphorylation of Syntaxin17 do not affect the interaction between Atg14 29
Phosphorylation of STX17 regulates SNARE complex assembly 30
Discussion 31
References 35
Appendix 47
Alers, S., Loffler, A. S., Wesselborg, S., & Stork, B. (2012). Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol, 32(1), 2-11. doi:10.1128/MCB.06159-11
Banerjee, R., Beal, M. F., & Thomas, B. (2010). Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications. Trends Neurosci, 33(12), 541-549. doi:10.1016/j.tins.2010.09.001
Barth, S., Glick, D., & Macleod, K. F. (2010). Autophagy: assays and artifacts. J Pathol, 221(2), 117-124. doi:10.1002/path.2694
Brocker, C., Engelbrecht-Vandre, S., & Ungermann, C. (2010). Multisubunit tethering complexes and their role in membrane fusion. Curr Biol, 20(21), R943-952. doi:10.1016/j.cub.2010.09.015
Burman, C., & Ktistakis, N. T. (2010a). Autophagosome formation in mammalian cells. Semin Immunopathol, 32(4), 397-413. doi:10.1007/s00281-010-0222-z
Burman, C., & Ktistakis, N. T. (2010b). Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett, 584(7), 1302-1312. doi:10.1016/j.febslet.2010.01.011
Cherra, S. J., 3rd, Kulich, S. M., Uechi, G., Balasubramani, M., Mountzouris, J., Day, B. W., & Chu, C. T. (2010). Regulation of the autophagy protein LC3 by phosphorylation. J Cell Biol, 190(4), 533-539. doi:10.1083/jcb.201002108
Cohen, P. (2002). The origins of protein phosphorylation. Nat Cell Biol, 4(5), E127-130. doi:10.1038/ncb0502-e127
Colecchia, D., Strambi, A., Sanzone, S., Iavarone, C., Rossi, M., Dall''Armi, C., . . . Chiariello, M. (2012). MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. Autophagy, 8(12), 1724-1740. doi:10.4161/auto.21857
Dascher, C., Matteson, J., & Balch, W. E. (1994). Syntaxin 5 regulates endoplasmic reticulum to Golgi transport. J Biol Chem, 269(47), 29363-29366.
Di Bartolomeo, S., Corazzari, M., Nazio, F., Oliverio, S., Lisi, G., Antonioli, M., . . . Fimia, G. M. (2010). The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J Cell Biol, 191(1), 155-168. doi:10.1083/jcb.201002100
Diao, J., Liu, R., Rong, Y., Zhao, M., Zhang, J., Lai, Y., . . . Zhong, Q. (2015). ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature, 520(7548), 563-566. doi:10.1038/nature14147
Eskelinen, E. L. (2005). Maturation of autophagic vacuoles in Mammalian cells. Autophagy, 1(1), 1-10.
Fader, C. M., Sanchez, D. G., Mestre, M. B., & Colombo, M. I. (2009). TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta, 1793(12), 1901-1916. doi:10.1016/j.bbamcr.2009.09.011
Fasshauer, D., Antonin, W., Subramaniam, V., & Jahn, R. (2002). SNARE assembly and disassembly exhibit a pronounced hysteresis. Nature Structural Biology, 9(2), 144-151. doi:DOI 10.1038/nsb750
Funderburk, S. F., Wang, Q. J., & Yue, Z. (2010). The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond. Trends Cell Biol, 20(6), 355-362. doi:10.1016/j.tcb.2010.03.002
Geng, J., & Klionsky, D. J. (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ''Protein modifications: beyond the usual suspects'' review series. EMBO Rep, 9(9), 859-864. doi:10.1038/embor.2008.163
Guo, B., Liang, Q., Li, L., Hu, Z., Wu, F., Zhang, P., . . . Zhang, H. (2014). O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat Cell Biol, 16(12), 1215-1226. doi:10.1038/ncb3066
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., . . . Shaw, R. J. (2008). AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell, 30(2), 214-226. doi:10.1016/j.molcel.2008.03.003
Haj, F. G., Verveer, P. J., Squire, A., Neel, B. G., & Bastiaens, P. I. (2002). Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science, 295(5560), 1708-1711. doi:10.1126/science.1067566
Hamasaki, M., Furuta, N., Matsuda, A., Nezu, A., Yamamoto, A., Fujita, N., . . . Yoshimori, T. (2013). Autophagosomes form at ER-mitochondria contact sites. Nature, 495(7441), 389-393. doi:10.1038/nature11910
He, C., & Klionsky, D. J. (2009). Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet, 43, 67-93. doi:10.1146/annurev-genet-102808-114910
He, C., & Levine, B. (2010). The Beclin 1 interactome. Curr Opin Cell Biol, 22(2), 140-149. doi:10.1016/j.ceb.2010.01.001
Hong, W. (2005). SNAREs and traffic. Biochim Biophys Acta, 1744(3), 493-517.
Itakura, E., Kishi-Itakura, C., & Mizushima, N. (2012). The Hairpin-type Tail-Anchored SNARE Syntaxin 17 Targets to Autophagosomes for Fusion with Endosomes/Lysosomes. Cell, 151(6), 1256-1269.
Jiang, P., Nishimura, T., Sakamaki, Y., Itakura, E., Hatta, T., Natsume, T., & Mizushima, N. (2014). The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. Mol Biol Cell, 25(8), 1327-1337. doi:10.1091/mbc.E13-08-0447
Johnson, L. N. (2009). The regulation of protein phosphorylation. Biochem Soc Trans, 37(Pt 4), 627-641. doi:10.1042/BST0370627
Kim, J., Kundu, M., Viollet, B., & Guan, K. L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol, 13(2), 132-141. doi:10.1038/ncb2152
Klionsky, D. J. (2005). The molecular machinery of autophagy: unanswered questions. J Cell Sci, 118(Pt 1), 7-18. doi:10.1242/jcs.01620
Kramer, L., & Ungermann, C. (2011). HOPS drives vacuole fusion by binding the vacuolar SNARE complex and the Vam7 PX domain via two distinct sites. Mol Biol Cell, 22(14), 2601-2611. doi:10.1091/mbc.E11-02-0104
Li, W. W., Li, J., & Bao, J. K. (2012). Microautophagy: lesser-known self-eating. Cell Mol Life Sci, 69(7), 1125-1136. doi:10.1007/s00018-011-0865-5
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B. H., & Jung, J. U. (2006). Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol, 8(7), 688-699. doi:10.1038/ncb1426
Lobingier, B. T., & Merz, A. J. (2012). Sec1/Munc18 protein Vps33 binds to SNARE domains and the quaternary SNARE complex. Mol Biol Cell, 23(23), 4611-4622. doi:10.1091/mbc.E12-05-0343
Lorenzen, J. A., Dadabay, C. Y., & Fischer, E. H. (1995). COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol, 131(3), 631-643.
Massey, A., Kiffin, R., & Cuervo, A. M. (2004). Pathophysiology of chaperone-mediated autophagy. Int J Biochem Cell Biol, 36(12), 2420-2434. doi:10.1016/j.biocel.2004.04.010
Mathew, R., Karantza-Wadsworth, V., & White, E. (2007). Role of autophagy in cancer. Nat Rev Cancer, 7(12), 961-967. doi:10.1038/nrc2254
May, A. P., Whiteheart, S. W., & Weis, W. I. (2001). Unraveling the mechanism of the vesicle transport ATPase NSF, the N-ethylmaleimide-sensitive factor. Journal of Biological Chemistry, 276(25), 21991-21994. doi:DOI 10.1074/jbc.R100013200
Mizushima, N., & Levine, B. (2010). Autophagy in mammalian development and differentiation. Nat Cell Biol, 12(9), 823-830. doi:10.1038/ncb0910-823
Moreau, K., Ravikumar, B., Renna, M., Puri, C., & Rubinsztein, D. C. (2011). Autophagosome precursor maturation requires homotypic fusion. Cell, 146(2), 303-317. doi:10.1016/j.cell.2011.06.023
Moreau, K., Renna, M., & Rubinsztein, D. C. (2013). Connections between SNAREs and autophagy. Trends Biochem Sci, 38(2), 57-63. doi:10.1016/j.tibs.2012.11.004
Muppirala, M., Gupta, V., & Swarup, G. (2011). Syntaxin 17 cycles between the ER and ERGIC and is required to maintain the architecture of ERGIC and Golgi. Biol Cell, 103(7), 333-350. doi:10.1042/BC20110006
Muppirala, M., Gupta, V., & Swarup, G. (2012). Tyrosine phosphorylation of a SNARE protein, syntaxin 17: implications for membrane trafficking in the early secretory pathway. Biochim Biophys Acta, 1823(12), 2109-2119. doi:10.1016/j.bbamcr.2012.09.003
Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., & Mann, M. (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell, 127(3), 635-648. doi:10.1016/j.cell.2006.09.026
Reggiori, F., & Klionsky, D. J. (2013). Autophagic Processes in Yeast: Mechanism, Machinery and Regulation. Genetics, 194(2), 341-361. doi:10.1534/genetics.112.149013
Renna, M., Schaffner, C., Winslow, A. R., Menzies, F. M., Peden, A. A., Floto, R. A., & Rubinsztein, D. C. (2011). Autophagic substrate clearance requires activity of the syntaxin-5 SNARE complex. J Cell Sci, 124(Pt 3), 469-482. doi:10.1242/jcs.076489
Rodkey, T. L., Liu, S., Barry, M., & McNew, J. A. (2008). Munc18a scaffolds SNARE assembly to promote membrane fusion. Mol Biol Cell, 19(12), 5422-5434. doi:10.1091/mbc.E08-05-0538
Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y.-Y., Kim, J., . . . Guan, K.-L. (2013). ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol, 15(7), 741-750. doi:10.1038/ncb2757
Sangwan, V., Abella, J., Lai, A., Bertos, N., Stuible, M., Tremblay, M. L., & Park, M. (2011). Protein-tyrosine phosphatase 1B modulates early endosome fusion and trafficking of Met and epidermal growth factor receptors. J Biol Chem, 286(52), 45000-45013. doi:10.1074/jbc.M111.270934
Shen, J., Tareste, D. C., Paumet, F., Rothman, J. E., & Melia, T. J. (2007). Selective activation of cognate SNAREpins by Sec1/Munc18 proteins. Cell, 128(1), 183-195. doi:10.1016/j.cell.2006.12.016
Tiganis, T., Kemp, B. E., & Tonks, N. K. (1999). The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling. J Biol Chem, 274(39), 27768-27775.
Ungar, D., & Hughson, F. M. (2003). SNARE protein structure and function. Annu Rev Cell Dev Biol, 19, 493-517. doi:10.1146/annurev.cellbio.19.110701.155609
Wani, W. Y., Boyer-Guittaut, M., Dodson, M., Chatham, J., Darley-Usmar, V., & Zhang, J. (2015). Regulation of autophagy by protein post-translational modification. Lab Invest, 95(1), 14-25. doi:10.1038/labinvest.2014.131
Wirth, M., Joachim, J., & Tooze, S. A. (2013). Autophagosome formation--the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage. Semin Cancer Biol, 23(5), 301-309. doi:10.1016/j.semcancer.2013.05.007
Alers, S., Loffler, A. S., Wesselborg, S., & Stork, B. (2012). Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol, 32(1), 2-11. doi:10.1128/MCB.06159-11
Angers, C. G., & Merz, A. J. (2011). New links between vesicle coats and Rab-mediated vesicle targeting. Semin Cell Dev Biol, 22(1), 18-26. doi:10.1016/j.semcdb.2010.07.003
Arasaki, K., Mikami, Y., Shames, S. R., Inoue, H., Wakana, Y., & Tagaya, M. (2017). Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17. Nature Communications, 8.
Arasaki, K., Shimizu, H., Mogari, H., Nishida, N., Hirota, N., Furuno, A., . . . Tagaya, M. (2015). A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division. Dev Cell, 32(3), 304-317. doi:10.1016/j.devcel.2014.12.011
Banerjee, R., Beal, M. F., & Thomas, B. (2010). Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications. Trends Neurosci, 33(12), 541-549. doi:10.1016/j.tins.2010.09.001
Barth, S., Glick, D., & Macleod, K. F. (2010). Autophagy: assays and artifacts. J Pathol, 221(2), 117-124. doi:10.1002/path.2694
Bennett, M. K., & Scheller, R. H. (1993). The molecular machinery for secretion is conserved from yeast to neurons. Proc Natl Acad Sci U S A, 90(7), 2559-2563.
Bjorge, J. D., Pang, A., & Fujita, D. J. (2000). Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J Biol Chem, 275(52), 41439-41446. doi:10.1074/jbc.M004852200
Brocker, C., Engelbrecht-Vandre, S., & Ungermann, C. (2010). Multisubunit tethering complexes and their role in membrane fusion. Curr Biol, 20(21), R943-952. doi:10.1016/j.cub.2010.09.015
Burgo, A., Casano, A. M., Kuster, A., Arold, S. T., Wang, G., Nola, S., . . . Galli, T. (2013). Increased activity of the vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor TI-VAMP/VAMP7 by tyrosine phosphorylation in the Longin domain. J Biol Chem, 288(17), 11960-11972. doi:10.1074/jbc.M112.415075
Burman, C., & Ktistakis, N. T. (2010a). Autophagosome formation in mammalian cells. Semin Immunopathol, 32(4), 397-413. doi:10.1007/s00281-010-0222-z
Burman, C., & Ktistakis, N. T. (2010b). Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett, 584(7), 1302-1312. doi:10.1016/j.febslet.2010.01.011
Dascher, C., Matteson, J., & Balch, W. E. (1994). Syntaxin 5 regulates endoplasmic reticulum to Golgi transport. J Biol Chem, 269(47), 29363-29366.
Di Bartolomeo, S., Corazzari, M., Nazio, F., Oliverio, S., Lisi, G., Antonioli, M., . . . Fimia, G. M. (2010). The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J Cell Biol, 191(1), 155-168. doi:10.1083/jcb.201002100
Diao, J., Liu, R., Rong, Y., Zhao, M., Zhang, J., Lai, Y., . . . Zhong, Q. (2015). ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature, 520(7548), 563-566. doi:10.1038/nature14147
Dietrich, L. E., Boeddinghaus, C., LaGrassa, T. J., & Ungermann, C. (2003). Control of eukaryotic membrane fusion by N-terminal domains of SNARE proteins. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1641(2), 111-119.
Dulubova, I., Sugita, S., Hill, S., Hosaka, M., Fernandez, I., Sudhof, T. C., & Rizo, J. (1999). A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J, 18(16), 4372-4382. doi:10.1093/emboj/18.16.4372
Eskelinen, E. L. (2005). Maturation of autophagic vacuoles in Mammalian cells. Autophagy, 1(1), 1-10.
Fader, C. M., Sanchez, D. G., Mestre, M. B., & Colombo, M. I. (2009). TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta, 1793(12), 1901-1916. doi:10.1016/j.bbamcr.2009.09.011
Fasshauer, D., Antonin, W., Subramaniam, V., & Jahn, R. (2002). SNARE assembly and disassembly exhibit a pronounced hysteresis. Nature Structural Biology, 9(2), 144-151. doi:DOI 10.1038/nsb750
Foletti, D. L., Lin, R., Finley, M. A., & Scheller, R. H. (2000). Phosphorylated syntaxin 1 is localized to discrete domains along a subset of axons. J Neurosci, 20(12), 4535-4544.
Foster, L. J., Yeung, B., Mohtashami, M., Ross, K., Trimble, W. S., & Klip, A. (1998). Binary interactions of the SNARE proteins syntaxin-4, SNAP23, and VAMP-2 and their regulation by phosphorylation. Biochemistry, 37(31), 11089-11096. doi:10.1021/bi980253t
Fu, J., Naren, A. P., Gao, X., Ahmmed, G. U., & Malik, A. B. (2005). Protease-activated receptor-1 activation of endothelial cells induces protein kinase Calpha-dependent phosphorylation of syntaxin 4 and Munc18c: role in signaling p-selectin expression. J Biol Chem, 280(5), 3178-3184. doi:10.1074/jbc.M410044200
Funderburk, S. F., Wang, Q. J., & Yue, Z. (2010). The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond. Trends Cell Biol, 20(6), 355-362. doi:10.1016/j.tcb.2010.03.002
Furuta, N., Fujita, N., Noda, T., Yoshimori, T., & Amano, A. (2010). Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol Biol Cell, 21(6), 1001-1010. doi:10.1091/mbc.E09-08-0693
Ganley, I. G., Wong, P. M., Gammoh, N., & Jiang, X. (2011). Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest. Mol Cell, 42(6), 731-743. doi:10.1016/j.molcel.2011.04.024
Geng, J., & Klionsky, D. J. (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ''Protein modifications: beyond the usual suspects'' review series. EMBO Rep, 9(9), 859-864. doi:10.1038/embor.2008.163
Guo, B., Liang, Q., Li, L., Hu, Z., Wu, F., Zhang, P., . . . Zhang, H. (2014). O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat Cell Biol, 16(12), 1215-1226. doi:10.1038/ncb3066
Gurunathan, S., Marash, M., Weinberger, A., & Gerst, J. E. (2002). t-SNARE phosphorylation regulates endocytosis in yeast. Mol Biol Cell, 13(5), 1594-1607. doi:10.1091/mbc.01-11-0541
Haj, F. G., Verveer, P. J., Squire, A., Neel, B. G., & Bastiaens, P. I. (2002). Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science, 295(5560), 1708-1711. doi:10.1126/science.1067566
Hamasaki, M., Furuta, N., Matsuda, A., Nezu, A., Yamamoto, A., Fujita, N., . . . Yoshimori, T. (2013). Autophagosomes form at ER-mitochondria contact sites. Nature, 495(7441), 389-393. doi:10.1038/nature11910
He, C., & Klionsky, D. J. (2009). Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet, 43, 67-93. doi:10.1146/annurev-genet-102808-114910
He, C., & Levine, B. (2010). The Beclin 1 interactome. Curr Opin Cell Biol, 22(2), 140-149. doi:10.1016/j.ceb.2010.01.001
Hong, W. (2005). SNAREs and traffic. Biochim Biophys Acta, 1744(3), 493-517.
Hubert, V., Peschel, A., Langer, B., Groger, M., Rees, A., & Kain, R. (2016). LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes. Biol Open, 5(10), 1516-1529. doi:10.1242/bio.018648
Huynh, H., Bottini, N., Williams, S., Cherepanov, V., Musumeci, L., Saito, K., . . . Kruger, J. (2004). Control of vesicle fusion by a tyrosine phosphatase. Nat Cell Biol, 6(9), 831-839.
Huynh, H., Bottini, N., Williams, S., Cherepanov, V., Musumeci, L., Saito, K., . . . Mustelin, T. (2004). Control of vesicle fusion by a tyrosine phosphatase. Nat Cell Biol, 6(9), 831-839. doi:10.1038/ncb1164
Itakura, E., Kishi-Itakura, C., & Mizushima, N. (2012). The Hairpin-type Tail-Anchored SNARE Syntaxin 17 Targets to Autophagosomes for Fusion with Endosomes/Lysosomes. Cell, 151(6), 1256-1269.
Jean, S., Cox, S., Nassari, S., & Kiger, A. A. (2015). Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome-lysosome fusion. EMBO Rep, 16(3), 297-311. doi:10.15252/embr.201439464
Jiang, P., Nishimura, T., Sakamaki, Y., Itakura, E., Hatta, T., Natsume, T., & Mizushima, N. (2014). The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. Mol Biol Cell, 25(8), 1327-1337. doi:10.1091/mbc.E13-08-0447
Khvotchev, M., Dulubova, I., Sun, J., Dai, H., Rizo, J., & Südhof, T. C. (2007). Dual Modes of Munc18-1/SNARE Interactions Are Coupled by Functionally Critical Binding to Syntaxin-1 N Terminus. The Journal of Neuroscience, 27(45), 12147-12155. doi:10.1523/jneurosci.3655-07.2007
Kim, J., Kundu, M., Viollet, B., & Guan, K. L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol, 13(2), 132-141. doi:10.1038/ncb2152
Klionsky, D. J. (2005). The molecular machinery of autophagy: unanswered questions. J Cell Sci, 118(Pt 1), 7-18. doi:10.1242/jcs.01620
Kramer, L., & Ungermann, C. (2011). HOPS drives vacuole fusion by binding the vacuolar SNARE complex and the Vam7 PX domain via two distinct sites. Mol Biol Cell, 22(14), 2601-2611. doi:10.1091/mbc.E11-02-0104
Li, M., Khambu, B., Zhang, H., Kang, J. H., Chen, X., Chen, D., . . . Yin, X. M. (2013). Suppression of lysosome function induces autophagy via a feedback down-regulation of MTOR complex 1 (MTORC1) activity. J Biol Chem, 288(50), 35769-35780. doi:10.1074/jbc.M113.511212
Li, W. W., Li, J., & Bao, J. K. (2012). Microautophagy: lesser-known self-eating. Cell Mol Life Sci, 69(7), 1125-1136. doi:10.1007/s00018-011-0865-5
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B. H., & Jung, J. U. (2006). Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol, 8(7), 688-699. doi:10.1038/ncb1426
Liu, X., Heidelberger, R., & Janz, R. (2014). Phosphorylation of syntaxin 3B by CaMKII regulates the formation of t-SNARE complexes. Mol Cell Neurosci, 60, 53-62. doi:10.1016/j.mcn.2014.03.002
Lobingier, B. T., & Merz, A. J. (2012). Sec1/Munc18 protein Vps33 binds to SNARE domains and the quaternary SNARE complex. Mol Biol Cell, 23(23), 4611-4622. doi:10.1091/mbc.E12-05-0343
Lorenzen, J. A., Dadabay, C. Y., & Fischer, E. H. (1995). COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol, 131(3), 631-643.
Ma, C., Li, W., Xu, Y., & Rizo, J. (2011). Munc13 mediates the transition from the closed syntaxin-Munc18 complex to the SNARE complex. Nat Struct Mol Biol, 18(5), 542-549. doi:10.1038/nsmb.2047
Majeed, M., Caveggion, E., Lowell, C. A., & Berton, G. (2001). Role of Src kinases and Syk in Fcgamma receptor-mediated phagocytosis and phagosome-lysosome fusion. J Leukoc Biol, 70(5), 801-811.
Massey, A., Kiffin, R., & Cuervo, A. M. (2004). Pathophysiology of chaperone-mediated autophagy. Int J Biochem Cell Biol, 36(12), 2420-2434. doi:10.1016/j.biocel.2004.04.010
Mathew, R., Karantza-Wadsworth, V., & White, E. (2007). Role of autophagy in cancer. Nat Rev Cancer, 7(12), 961-967. doi:10.1038/nrc2254
Matos, M. F., Mukherjee, K., Chen, X., Rizo, J., & Sudhof, T. C. (2003). Evidence for SNARE zippering during Ca2+-triggered exocytosis in PC12 cells. Neuropharmacology, 45(6), 777-786.
Matveeva, E. A., Whiteheart, S. W., Vanaman, T. C., & Slevin, J. T. (2001). Phosphorylation of the N-ethylmaleimide-sensitive factor is associated with depolarization-dependent neurotransmitter release from synaptosomes. Journal of Biological Chemistry, 276(15), 12174-12181.
May, A. P., Whiteheart, S. W., & Weis, W. I. (2001). Unraveling the mechanism of the vesicle transport ATPase NSF, the N-ethylmaleimide-sensitive factor. Journal of Biological Chemistry, 276(25), 21991-21994. doi:DOI 10.1074/jbc.R100013200
McLelland, G. L., Lee, S. A., McBride, H. M., & Fon, E. A. (2016). Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system. J Cell Biol, 214(3), 275-291. doi:10.1083/jcb.201603105
Mizushima, N., & Levine, B. (2010). Autophagy in mammalian development and differentiation. Nat Cell Biol, 12(9), 823-830. doi:10.1038/ncb0910-823
Monteleone, M. C., Gonzalez Wusener, A. E., Burdisso, J. E., Conde, C., Caceres, A., & Arregui, C. O. (2012). ER-bound protein tyrosine phosphatase PTP1B interacts with Src at the plasma membrane/substrate interface. PLoS One, 7(6), e38948. doi:10.1371/journal.pone.0038948
Moreau, K., Ravikumar, B., Renna, M., Puri, C., & Rubinsztein, D. C. (2011). Autophagosome precursor maturation requires homotypic fusion. Cell, 146(2), 303-317. doi:10.1016/j.cell.2011.06.023
Moreau, K., Renna, M., & Rubinsztein, D. C. (2013). Connections between SNAREs and autophagy. Trends Biochem Sci, 38(2), 57-63. doi:10.1016/j.tibs.2012.11.004
Muppirala, M., Gupta, V., & Swarup, G. (2011). Syntaxin 17 cycles between the ER and ERGIC and is required to maintain the architecture of ERGIC and Golgi. Biol Cell, 103(7), 333-350. doi:10.1042/BC20110006
Muppirala, M., Gupta, V., & Swarup, G. (2012). Tyrosine phosphorylation of a SNARE protein, syntaxin 17: implications for membrane trafficking in the early secretory pathway. Biochim Biophys Acta, 1823(12), 2109-2119. doi:10.1016/j.bbamcr.2012.09.003
Pal, R., Palmieri, M., Loehr, J. A., Li, S., Abo-Zahrah, R., Monroe, T. O., . . . Rodney, G. G. (2014). Src-dependent impairment of autophagy by oxidative stress in a mouse model of Duchenne muscular dystrophy. Nat Commun, 5, 4425. doi:10.1038/ncomms5425
Peng, C., Ye, J., Yan, S., Kong, S., Shen, Y., Li, C., . . . Tao, W. (2012). Ablation of vacuole protein sorting 18 (Vps18) gene leads to neurodegeneration and impaired neuronal migration by disrupting multiple vesicle transport pathways to lysosomes. J Biol Chem, 287(39), 32861-32873. doi:10.1074/jbc.M112.384305
Rapaport, D., Lugassy, Y., Sprecher, E., & Horowitz, M. (2010). Loss of SNAP29 impairs endocytic recycling and cell motility. PLoS One, 5(3), e9759. doi:10.1371/journal.pone.0009759
Rathore, S. S., Bend, E. G., Yu, H., Hammarlund, M., Jorgensen, E. M., & Shen, J. (2010). Syntaxin N-terminal peptide motif is an initiation factor for the assembly of the SNARE-Sec1/Munc18 membrane fusion complex. Proc Natl Acad Sci U S A, 107(52), 22399-22406. doi:10.1073/pnas.1012997108
Reggiori, F., & Klionsky, D. J. (2013). Autophagic Processes in Yeast: Mechanism, Machinery and Regulation. Genetics, 194(2), 341-361. doi:10.1534/genetics.112.149013
Renna, M., Schaffner, C., Winslow, A. R., Menzies, F. M., Peden, A. A., Floto, R. A., & Rubinsztein, D. C. (2011). Autophagic substrate clearance requires activity of the syntaxin-5 SNARE complex. J Cell Sci, 124(Pt 3), 469-482. doi:10.1242/jcs.076489
Rieder, S. E., & Emr, S. D. (1997). A novel RING finger protein complex essential for a late step in protein transport to the yeast vacuole. Mol Biol Cell, 8(11), 2307-2327.
Rizo, J., & Xu, J. (2015). The Synaptic Vesicle Release Machinery. Annu Rev Biophys, 44, 339-367. doi:10.1146/annurev-biophys-060414-034057
Rodkey, T. L., Liu, S., Barry, M., & McNew, J. A. (2008). Munc18a scaffolds SNARE assembly to promote membrane fusion. Mol Biol Cell, 19(12), 5422-5434. doi:10.1091/mbc.E08-05-0538
Rothman, J. E., & Warren, G. (1994). Implications of the SNARE hypothesis for intracellular membrane topology and dynamics. Curr Biol, 4(3), 220-233.
Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y.-Y., Kim, J., . . . Guan, K.-L. (2013). ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol, 15(7), 741-750. doi:10.1038/ncb2757
Sangwan, V., Abella, J., Lai, A., Bertos, N., Stuible, M., Tremblay, M. L., & Park, M. (2011). Protein-tyrosine phosphatase 1B modulates early endosome fusion and trafficking of Met and epidermal growth factor receptors. J Biol Chem, 286(52), 45000-45013. doi:10.1074/jbc.M111.270934
Sato, M., Saegusa, K., Sato, K., Hara, T., Harada, A., & Sato, K. (2011). Caenorhabditis elegans SNAP-29 is required for organellar integrity of the endomembrane system and general exocytosis in intestinal epithelial cells. Mol Biol Cell, 22(14), 2579-2587. doi:10.1091/mbc.E11-04-0279
Schardt, A., Brinkmann, B. G., Mitkovski, M., Sereda, M. W., Werner, H. B., & Nave, K. A. (2009). The SNARE protein SNAP-29 interacts with the GTPase Rab3A: Implications for membrane trafficking in myelinating glia. J Neurosci Res, 87(15), 3465-3479. doi:10.1002/jnr.22005
Seals, D. F., Eitzen, G., Margolis, N., Wickner, W. T., & Price, A. (2000). A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion. Proc Natl Acad Sci U S A, 97(17), 9402-9407.
Shen, H. M., & Mizushima, N. (2014). At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy. Trends Biochem Sci, 39(2), 61-71. doi:10.1016/j.tibs.2013.12.001
Shen, J., Tareste, D. C., Paumet, F., Rothman, J. E., & Melia, T. J. (2007). Selective activation of cognate SNAREpins by Sec1/Munc18 proteins. Cell, 128(1), 183-195. doi:10.1016/j.cell.2006.12.016
Shuang, R., Zhang, L., Fletcher, A., Groblewski, G. E., Pevsner, J., & Stuenkel, E. L. (1998). Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings. J Biol Chem, 273(9), 4957-4966.
Snyder, D. A., Kelly, M. L., & Woodbury, D. J. (2006). SNARE complex regulation by phosphorylation. Cell Biochem Biophys, 45(1), 111-123. doi:10.1385/CBB:45:1:111
Sollner, T., Whiteheart, S. W., Brunner, M., Erdjument-Bromage, H., Geromanos, S., Tempst, P., & Rothman, J. E. (1993). SNAP receptors implicated in vesicle targeting and fusion. Nature, 362(6418), 318-324. doi:10.1038/362318a0
Su, Q., Mochida, S., Tian, J. H., Mehta, R., & Sheng, Z. H. (2001). SNAP-29: a general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission. Proc Natl Acad Sci U S A, 98(24), 14038-14043. doi:10.1073/pnas.251532398
Takats, S., Nagy, P., Varga, A., Pircs, K., Karpati, M., Varga, K., . . . Juhasz, G. (2013). Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila. J Cell Biol, 201(4), 531-539. doi:10.1083/jcb.201211160
Teng, F. Y., Wang, Y., & Tang, B. L. (2001). The syntaxins. Genome Biol, 2(11),REVIEWS3012.
Tian, J.-H., Das, S., & Sheng, Z.-H. (2003). Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18. Journal of Biological Chemistry, 278(28), 26265-26274.
Tiganis, T., Kemp, B. E., & Tonks, N. K. (1999). The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling. J Biol Chem, 274(39), 27768-27775.
Trost, M., English, L., Lemieux, S., Courcelles, M., Desjardins, M., & Thibault, P. (2009). The phagosomal proteome in interferon-γ-activated macrophages. Immunity, 30(1), 143-154.
Ungar, D., & Hughson, F. M. (2003). SNARE protein structure and function. Annu Rev Cell Dev Biol, 19, 493-517. doi:10.1146/annurev.cellbio.19.110701.155609
Weinberger, A., Kamena, F., Kama, R., Spang, A., & Gerst, J. E. (2005). Control of Golgi morphology and function by Sed5 t-SNARE phosphorylation. Mol Biol Cell, 16(10), 4918-4930. doi:10.1091/mbc.E05-02-0101
Wu, Z., Chang, P. C., Yang, J. C., Chu, C. Y., Wang, L. Y., Chen, N. T., . . . Kung, H. J. (2010). Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors. Genes Cancer, 1(1), 40-49. doi:10.1177/1947601909358324
Wurmser, A. E., Sato, T. K., & Emr, S. D. (2000). New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. J Cell Biol, 151(3), 551-562.
Yu, L., McPhee, C. K., Zheng, L., Mardones, G. A., Rong, Y., Peng, J., . . . Lenardo, M. J. (2010). Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature, 465(7300), 942-946. doi:10.1038/nature09076
Zhao, C., Slevin, J. T., & Whiteheart, S. W. (2007). Cellular functions of NSF: not just SNAPs and SNAREs. FEBS Lett, 581(11), 2140-2149. doi:10.1016/j.febslet.2007.03.032


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top