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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃偉邦(Wei-Pang Huang) | |
| dc.contributor.author | Yun-Ling Chen | en |
| dc.contributor.author | 陳昀伶 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:29:42Z | - |
| dc.date.available | 2018-08-27 | |
| dc.date.copyright | 2013-08-27 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-15 | |
| dc.identifier.citation | Baehrecke, E.H. (2005). Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol 6, 505-510.
Bergamini, E., Cavallini, G., Donati, A., and Gori, Z. (2003). The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically. Biomed Pharmacother 57, 203-208. Bhatia, V. K., Madsen, K. L., Bolinger, P. Y., Kunding, A., Hedegard, P., Gether, U.,and Stamou, D. (2009). Amphipathic motifs in BAR domains are essential for membrane curvature sensing. EMBO J. 28(21), 3303-3314. Blood, P. D., Voth, G. A. (2006) Direct observation of Bin/amphiphysin/Rvs (BAR) domain-induced membrane curvature by means of molecular dynamics simulations. Proc Natl Acad Sci U S A. 103(41),15068-15072. Bolender, R.P., and Weibel, E.R. (1973). A morphometric study of the removal of phenobarbital-induced membranes from hepatocytes after cessation of threatment. J Cell Biol 56, 746-761. Campelo, F., McMahon, H. T., and Kozlov, M. M. (2008) The hydrophobic insertion mechanism of membrane curvature generation by proteins. Biophys J. 95, 2325-39. Cebollero, E., and Reggiori, F. (2009). Regulation of autophagy in yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1793, 1413-1421. Cebollero, E., van der Vaart, A., Zhao, M., Rieter, E., Klionsky, D. J., Helms, J. B., Reggiori, F. (2012) Phosphatidylinositol-3-phosphate clearance plays a key role in autophagosome completion. Curr Biol. 22, 1545-1553. Cheng, N.Y. (2011). Characterization of the role of Atg24 in autophagy regulation in Saccharomyces cerevisiae. Master thesis. National Taiwan University, Taipei City, Taiwan, ROC. Cheong, H., Yorimitsu, T., Reggiori, F., Legakis, J.E., Wang, C.W., and Klionsky, D.J. (2005). Atg17 regulates the magnitude of the autophagic response. Mol Biol Cell 16, 3438-3453. Ciechanover, A. (2005). Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6, 79-87. Clark S.L. Jr. (1957). Cellular differentiation in the kidneys of newborn mice studies with the electron microscope. J Biophys Biochem Cytol. 3, 349-362. Codogno, P., and Meijer, A.J. (2005). Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12 Suppl 2, 1509-1518. Conibear, E., Stevens, T.H. (1998). Multiple sorting pathways between the late Golgi and the vacuole in yeast. Biochim Biophys Acta. 1404, 211-230. Cullen, P.J. (2008). Endosomal sorting and signalling: an emerging role for sorting nexins. Nature Reviews Molecular Cell Biology 9, 574-582. Cui, H., Ayton, G. S., Voth, G. A. (2009). Membrane binding by the endophilin N-BAR domain. Biophys J. 97(10), 2746-2753. Darsow, T., Rieder, S.E., Emr, S.D. (1997) A multispecificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. J Cell Biol. 138, 517-29. De Duve, C., and Wattiaux, R. (1966). Functions of lysosomes. Annu Rev Physiol 28, 435-492. Gautier, R., Douguet, D., Antonny, B.,and Drin, G. (2008) HELIQUEST: a web server to screen sequences with specific alpha-helical properties. Bioinformatics 24(18), 2101-2102. Gutierrez, M.G., Master, S.S., Singh, S.B., Taylor, G.A., Colombo, M.I., and Deretic, V. (2004). Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753-766. Haft, C.R., de la Luz Sierra, M., Barr, V.A., Haft, D.H., and Taylor, S.I. (1998). Identification of a family of sorting nexin molecules and characterization of their association with receptors. Mol Cell Biol 18, 7278-7287. Hamasaki, M., Furuta, N., Matsuda, A., Nezu, A., Yamamoto, A., Fujita, N., Oomori, H., Noda, T., Haraguchi, T., Hiraoka, Y., Amano, A., and Yoshimori, T. (2013). Autophagosomes form at ER-mitochondria contact sites. Nature. 495, 389-393. Hamasaki, M., Noda, T., and Ohsumi, Y. (2005). Starvation triggers the delivery of the endoplasmic reticulum to the vacuole via autophagy in yeast. Traffic 6, 56-65. Harding, T.M., Hefner-Gravink, A., Thumm, M., and Klionsky, D.J. (1996). Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway. J Biol Chem 271, 17621-17624. He, C. and Klionsky, D.J. (2006) Autophagy and neurodegeneration. ACS Chem Biol. 1, 211-213. Hershko, A., and Ciechanover, A. (1998). The ubiquitin system. Annu Rev Biochem 67, 425-479. Hettema, E.H., Lewis, M.J., Black, M.W., and Pelham, H.R. (2003). Retromer and the sorting nexins Snx4/41/42 mediate distinct retrieval pathways from yeast endosomes. EMBO J 22, 548-557. Hochstrasser, M. (1996). Ubiquitin-dependent protein degradation. Annu Rev Genet. 30, 405-439. Hsieh, Y.J. (2011). The role of Atg20 in the regulation of selective autophagy pathways. Master thesis. National Taiwan University, Taipei City, Taiwan, ROC. Hutchins, M.U. and Klionsky, D.J. (2001). Vacuolar localization of oligomeric alpha-mannosidase requires the cytoplasm to vacuole targeting and autophagy pathway components in Saccharomyces cerevisiae. J Biol Chem. 276, 20491-20498. Hutchins, M.U., Veenhuis, M., and Klionsky, D.J. (1999). Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway. J Cell Sci 112 ( Pt 22), 4079-4087. James, P., Halladay, J., and Craig, E.A. (1996). Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics 144, 1425-1436. Juhasz, G., Hill, J.H., Yan, Y., Sass, M., Baehrecke, E.H., Backer, J.M., and Neufeld, T.P. (2008). The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol 181, 655-666. Kanki, T., and Klionsky, D.J. (2008). Mitophagy in yeast occurs through a selective mechanism. J Biol Chem 283, 32386-32393. Kihara A, Noda T, Ishihara N, Ohsumi Y (2001) Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol 152, 519–530 Kim, J., Rodriguez-Enriquez, S., and Lemasters, J.J. (2007). Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462, 245-253. Kim, J., Huang, W.P., and Klionsky, D.J. (2001a). Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol 152, 51-64. Kim, J., Huang, W.P., Stromhaug, P.E., and Klionsky, D.J. (2002). Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation. J Biol Chem. 277, 763-773. Kim, J., Kamada, Y., Stromhaug, P.E., Guan, J., Hefner-Gravink, A., Baba, M., Scott, S.V., Ohsumi, Y., Dunn, W.A., Jr., and Klionsky, D.J. (2001b). Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole. J Cell Biol 153, 381-396. Klionsky, D.J. (2005). The molecular machinery of autophagy: unanswered questions. J Cell Sci 118, 7-18. Klionsky, D.J., Cregg, J.M., Dunn, W.A. Jr., Emr, S.D., Sakai, Y., Sandoval, I.V., Sibirny, A., Subramani, S., Thumm, M., Veenhuis, M., and Ohsumi, Y. (2003). A unified nomenclature for yeast autophagy-related genes. Dev Cell. 5, 539-545. Klionsky, D.J., Cueva, R., and Yaver, D.S. (1992). Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. J Cell Biol 119, 287-299. Klionsky, D.J., and Emr, S.D. (1990). A new class of lysosomal/vacuolar protein sorting signals. J Biol Chem. 265, 5349-5352. Klionsky, D.J. and Ohsumi, Y. (1999). Vacuolar import of proteins and organelles from the cytoplasm. Annu Rev Cell Dev Biol. 15, 1-32. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 441, 880-884. Komatsu, M., Waguri, S., Koike, M., Sou, Y.S., Ueno, T., Hara, T., Mizushima, N., Iwata, J., Ezaki, J., Murata, S., et al. (2007). Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149-1163. Kopitz, J., Kisen, G.O., Gordon, P.B., Bohley, P., and Seglen, P.O. (1990). Nonselective autophagy of cytosolic enzymes by isolated rat hepatocytes. J Cell Biol. 111, 941-953. Kourtis, N. and Tavernarakis, N. (2009). Autophagy and cell death in model organisms. Cell Death Differ. 16, 21-30. Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T.,and Mizushima, N. (2004). The role of autophagy during the early neonatal starvation period. Nature. 432, 1032-1036. Levine, B., and Klionsky, D.J. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6, 463-477. Levine, B. and Kroemer, G. (2008). Autophagy in the pathogenesis of disease. Cell. 132, 27-42. Longtine, M.S., McKenzie, A., 3rd, Demarini, D.J., Shah, N.G., Wach, A., Brachat, A., Philippsen, P., and Pringle, J.R. (1998). Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14, 953-961. Lum J.J., Bauer, D.E., Kong, M., Harris, M.H., Li, C., Lindsten, T., and Thompson, C.B. (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 120, 237-48. Lynch-Day, M.A. and Klionsky, D.J. (2010). The Cvt pathway as a model for selective autophagy. FEBS Lett 584, 1359-1366. Madeo, F., Eisenberg, T., and Kroemer, G. (2009). Autophagy for the avoidance of neurodegeneration. Genes Dev 23, 2253-2259. Marchler-Bauer A,, Zheng C., Chitsaz, F., Derbyshire, M. K., Geer, L. Y., Geer, R. C., Gonzales, N. R., Gwadz, M., Hurwitz, D. I., Lanczycki, C. J., Lu, F., Lu, S., Marchler, G. H., Song, J. S., Thanki, N., Yamashita, R. A., Zhang D., and Bryant, S. H. (2013). CDD: conserved domains and protein three-dimensional structure. Nucleic Acids Res. 41, D348-D352. Marcusson, E.G., Horazdovsky, B.F., Cereghino, J.L., Gharakhanian, E., Emr, S.D. (1994) The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene. Cell. 77, 579-86. Marino, G. and Lopez-Otin, C. (2008). Autophagy and aging: new lessons from progeroid mice. Autophagy 4, 807-809. Masuda, M., Takeda, S., Sone, M., Ohki, T., Mori, H., Kamioka, Y., Mochizuki, N. (2006). Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms. EMBO J. 25(12), 2889-2897. Mathew, R., Karantza-Wadsworth, V., and White, E. (2007). Role of autophagy in cancer. Nat Rev Cancer 7, 961-967. Melendez A, Neufeld TP. (2008). The cell biology of autophagy in metazoans: a developing story. Development. 135, 2347-2360. Melinda, A., Lynch-Day, M.A., and Klionsky, D.J. (2010). The Cvt pathway as a model for selective autophagy. FEBS Lett. 584, 1359-1366. Mijaljica, D., Prescott, M., Klionsky, D.J., and Devenish, R.J. (2007). Autophagy and vacuole homeostasis: a case for self-degradation? Autophagy 3, 417-421. Mizushima, N., Levine, B., Cuervo, A.M., and Klionsky, D.J. (2008). Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075. Motley, A.M., Nuttall, J.M., Hettema, E.H. (2012). Atg36: the Saccharomyces cerevisiae receptor for pexophagy. Autophagy. 8, 1680-1681. Nice, D.C., Sato, T.K., Stromhaug, P.E., Emr, S.D., and Klionsky, D.J. (2002). Cooperative binding of the cytoplasm to vacuole targeting pathway proteins, Cvt13 and Cvt20, to phosphatidylinositol 3-phosphate at the pre-autophagosomal structure is required for selective autophagy. J Biol Chem 277, 30198-30207. Onodera, J., and Ohsumi, Y. (2005). Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation. J Biol Chem 280, 31582-31586. Peter, B. J., Kent, H. M., Mills, I. G., Vallis, Y., Butler, P. J. G., Evans, P. R., andM cMahon, H. T. (2004) BAR Domains as Sensors of Membrane Curvature: The Amphiphysin BAR Structure. Science 303, 495-499. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., Ferrin, T. E. (2004) UCSF Chimera—A Visualization System for Exploratory Research and Analysis. J Comput Chem 25, 1605–1612. Pierce, B.G., Hourai, Y., Weng, Z. (2011) Accelerating Protein Docking in ZDOCK Using an Advanced 3D Convolution Library. PLoS One 6(9), e24657. Pylypenko, O., Lundmark, R., Rasmuson, E., Carlsson, S.R., and Rak, A. (2007). The PX-BAR membrane-remodeling unit of sorting nexin 9. The EMBO Journal 26, 4788–4800. Rao, Y. and Haucke, V. (2011). Membrane shaping by the Bin/amphiphysin/Rvs (BAR) domain protein superfamily. Cell Mol Life Sci. 68(24), 3983-3993. Reggiori, F. and Klionsky, D.J. (2002). Autophagy in the eukaryotic cell. Eukaryot Cell 1, 11-21. Rogers, S.W. and Rechsteiner, M. (1988) Degradation of structurally characterized proteins injected into HeLa cells. Effects of intracellular location and the involvement of lysosomes. J Biol Chem. 263, 19843-19849. Rosenfeldt, M.T., and Ryan, K.M. (2011). The multiple roles of autophagy in cancer. Carcinogenesis. Roy, A., Kucukural, A., and Zhang, Y., (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols 5, 725-738. Sakai, Y., Oku, M., van der Klei, I.J., and Kiel, J.A. (2006). Pexophagy: autophagic degradation of peroxisomes. Biochim Biophys Acta 1763, 1767-1775. Scott, S.V., Baba, M., Ohsumi, Y., and Klionsky, D. J. (1996). Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular mechanism. J Cell Biol. 138, 37-44. Scott, S.V., Klionsky, D. J. (1995) In vitro reconstitution of cytoplasm to vacuole protein targeting in yeast. J Cell Biol. 131, 1727-1735. Scott, S.V., Guan, J., Hutchins, M.U., Kim, J., and Klionsky, D.J. (2001). Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. Mol Cell 7, 1131-1141. Scott, S.V., Hefner-Gravink, A., Morano, K.A., Noda, T., Ohsumi, Y., and Klionsky, D.J. (1996). Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole. Proc Natl Acad Sci U S A 93, 12304-12308. Seaman, M.N.J. (2008). Endosome protein sorting: motifs and machinery. Cellular and Molecular Life Sciences 65, 2842-2858. Seaman, M. N., Marcusson, E. G., Cereghino, J. L., Emr, S. D. (1997) Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol. 137, 79-92. Seet, L.F., and Hong, W.J. (2006). The Phox (PX) domain proteins and membrane traffic. Biochim Biophys Acta Mol Cell Biol Lipids 1761, 878-896. Seglen P. O., and Bohley, P. (1992). Autophagy and other vacuolar protein degradation mechanisms. Experientia 48, 158-172 Shimada, A., Niwa, H., Tsujita, K., Suetsugu, S., Nitta, K., Hanawa-Suetsugu, K., Akasaka, R., Nishino, Y., Toyama, M., Chen, L., Liu, Z. J., Wang, B. C., Yamamoto, M., Terada, T., Miyazawa, A., Tanaka, A., Sugano, S., Shirouzu, M., Nagayama, K., Takenawa, T.,and Yokoyama, S. (2007) Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell. 129(4), 761-72. Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C.B., and Tsujimoto, Y. (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 6, 1221-8. Shintani, T., Huang, W.P., Stromhaug, P.E., and Klionsky, D.J. (2002). Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. Dev Cell 3, 825-837. Shintani, T., and Klionsky, D.J. (2004a). Autophagy in health and disease: a double-edged sword. Science 306, 990-995. Shintani, T., and Klionsky, D.J. (2004b). Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. J Biol Chem 279, 29889-29894. Stack, J.H., DeWald, D.B., Takegawa, K., Emr, S.D. (1995) Vesicle-mediated protein transport: regulatory interactions between the Vps15 protein kinase and the Vps34 PtdIns 3-kinase essential for protein sorting to the vacuole in yeast. J Cell Biol. 129, 321-234. Suzuki, K., Kirisako, T., Kamada, Y., Mizushima, N., Noda, T., and Ohsumi, Y. (2001). The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J 20, 5971-5981. Suzuki, K., Kubota, Y., Sekito, T., and Ohsumi, Y. (2007). Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12, 209-218. Takeshige, K., Baba, M., Tsuboi, S., Noda, T., and Ohsumi, Y. (1992). Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119, 301-311. Tsukada, M., and Ohsumi, Y. (1993). Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333, 169-174. Tuttle, D.L., Lewin, A.S., and Dunn, W.A., Jr. (1993). Selective autophagy of peroxisomes in methylotrophic yeasts. Eur J Cell Biol 60, 283-290. Uetz, P., Giot, L., Cagney, G., Mansfield, T.A., Judson, R.S., Knight, J.R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., Qureshi-Emili, A., Li, Y., Godwin, B., Conover, D., Kalbfleisch, T., Vijayadamodar, G., Yang, M., Johnston, M., Fields, S., Rothberg, J.M. (2000) A comprehensive analysis ofprotein-protein interactions in Saccharomyces cerevisiae. Nature 403(6770), 623-627. Vida, T.A. and Emr, S.D. (1995). A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. The Journal of cell biology 128, 779-792. Vida, T.A., Huyer, G.,and Emr, S.D. (1993) Yeast vacuolar proenzymes are sorted in the late Golgi complex and transported to the vacuole via a prevacuolar endosome-like compartment. J Cell Biol. 121, 1245-1256. Wada, Y., Nakamura, N., Ohsumi, Y., and Hirata, A. (1997) Vam3p,a new member of Syntaxin related protein, is required for vacular assembly in the yeast Saccharomyces cerevisiae. J Cell Sci 110, 1299-1306. Wang, C.W., Kim, J., Huang, W.P., Abeliovich, H., Stromhaug, P.E., Dunn, W.A., Jr., and Klionsky, D.J. (2001a). Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy, and pexophagy pathways. J Biol Chem 276, 30442-30451. Winslow, A.R., and Rubinsztein, D.C. (2008). Autophagy in neurodegeneration and development. Biochim Biophys Acta 1782, 723-729. Xie, Z. and Klionsky, D.J. (2007). Autophagosome formation: core machinery and adaptations. Nat Cell Biol. 9, 1102-1109. Yang, Z., and Klionsky, D.J. (2010). Eaten alive: a history of macroautophagy. Nat Cell Biol 12, 814-822. Yang, Z.F., and Klionsky, D.J. (2009). An Overview of the Molecular Mechanism of Autophagy. Autophagy in Infection and Immunity 335, 1-32. Yorimitsu, T., and Klionsky, D.J. (2005). Atg11 links cargo to the vesicle-forming machinery in the cytoplasm to vacuole targeting pathway. Mol Biol Cell 16, 1593-1605. Yu, L., Alva, A., Su, H., Dutt, P., Freundt, E., Welsh, S., Baehrecke, E.H., and Lenardo, M.J. (2004). Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science. 304, 1500-1502. Yu, J.W., and Lemmon, M.A. (2001). All phox homology (PX) domains from Saccharomyces cerevisiae specifically recognize phosphatidylinositol 3-phosphate. J Biol Chem 276, 44179-44184. Yuga, M., Gomi, K., Klionsky, D.J., and Shintani, T. (2011). Aspartyl aminopeptidase is imported from the cytoplasm to the vacuole by selective autophagy in Saccharomyces cerevisiae. J Biol Chem. 286, 13704-13713. Zhang, Y., (2008). I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9, 40. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60776 | - |
| dc.description.abstract | 細胞自噬（autophagy）一直被認為是一種非選擇性分解大分子物質的機制，在養份缺乏的環境下，藉此維持細胞內的恆定性與生存，且在真核生物中具高度保守性。然而近年的研究發現，在出芽酵母菌細胞中存在著另一種具選擇性的機制，稱為細胞質至液胞傳遞途徑（cytoplasm-to-vacuole targeting pathway, Cvt pathway）。在養分充足的情況下，此途徑會將液胞水解酵素aminopeptidase1前驅物（prApe1）、α-mannosidase1（Ams1）以及aspartyl aminopeptidase（Ape4）運送至液胞。雖然前人的文獻已報告Atg20參與在細胞質至液胞傳遞途徑中，但其詳細的作用機制還不甚明瞭。此外，已知Atg20具有一個phox homology domain（PX domain），此PX domain 能專一性的與PI3P結合並藉此決定了Atg20在細胞中的分布，但此結合的親和性與其他同樣具有PX domain的蛋白質比較起來相對偏低，顯示可能有其他協助Atg20在細胞中分布的機制存在。本研究發現，Atg20蛋白的BAR（Bin/Amphiphysin/Rvs）結構性區域中的小片段缺損，會造成細胞質至液胞傳遞途徑無法完成以及內噬系統的運送缺失。進一步分析則發現，BAR結構性區域中的長段雙極性螺旋（Amphipathic helix L, AHL）以及其最末端49個胺基酸對於Atg20與Atg24移動到自噬體形成位置（pre-autophagosomal structure, PAS）以及Snc1在內噬系統中的回收是必須的。而失去了最後49胺基酸的Atg20更喪失了與Atg24的結合能力，並造成了減緩細胞增生速度的後果。另外，同時定點突變位於AHL中的Leu378和Ile382雖然不影響Atg20與膜的結合能力，但卻會使運輸小泡（Cvt vesicles）無法正常形成。最後，Atg20與Atg24須藉由Ymr1的幫助將PI3P去磷酸化後，才得以自PAS被釋回細胞質中。綜合以上所述，BAR結構性區域藉由不同的功能，影響細胞質至液胞傳遞途徑以及內膜傳遞系統（endomembrane trafficking）。此外，Atg20以及Atg24在運輸小泡形成後會從PAS被回收再利用。 | zh_TW |
| dc.description.abstract | Autophagy has been considered as a non-selective degradation process in order to maintain cellular homeostasis upon starvation for a long time. This physiological response is highly conserved in all eukaryotes. Recent studies have found that the cytoplasm-to-vacuole targeting (Cvt) pathway of the budding yeast is a selective type of autophagy, which constitutively transports prApe1, Ams1, and Ape4 to the vacuole under vegetative growth condition. Although Atg20 has been reported required for the Cvt pathway, how it participates in the control of the Cvt pathway remains largely unknown. Recent studies have shown that Atg20 contains a conserved phox homology domain (PX domain), which could specifically bind to PI3P for determining the distribution in the cells, but the affinity is relatively low. Here, I found that deletion of the Bin/Amphiphysin/Rvs (BAR) domain of Atg20 impairs its ability to regulate the Cvt pathway and endomembrane trafficking. I further showed that the long amphipathic helix (AHL) and the last 49 residues of Atg20 are essential for the localization of Atg20 and Atg24 to the pre-autophagosomal structure (PAS) and for the retrieval of Snc1 from the endocytic pathway. Moreover, lacking the last 49 residues affects its interaction with Atg24 and causes dominant-negative effects on proliferation. Formation of Cvt vesicles cannot complete when Leu378 and Ile382 in the AHL are simultaneously substituted for Glu, although this mutant protein still fractionates with vesicle membrane. Moreover, Atg20 and its partner protein, Atg24, need to be released from the PAS for reusing after PI3P is dephosphorylated by Ymr1. Taken together, these results suggest that the BAR domain of Atg20 regulates the Cvt pathway and endomembrane trafficking via multiple mechanisms, and Atg20 and Atg24 are recycled after the completion of Cvt vesicles formation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:29:42Z (GMT). No. of bitstreams: 1 ntu-102-R00b41017-1.pdf: 5297995 bytes, checksum: 11507a9c82d436c23e2595087812785a (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | CONTENTS
誌謝 ii 中文摘要 iv Abstract v Chapter 1: Introduction 1 1.1 Overview of autophagy 3 1.2 Overview of the Cvt pathway 4 1.3 The molecular mechanism of the Cvt pathway 6 1.4 The role of Atg20 in the Cvt pathway and the endomembrane trafficking 7 Chapter 2: Materials and Methods 10 2.1 Strains and media 10 2.2 Plasmids construction 11 2.3 Preparation of whole cell extracts for immunoblot analysis 12 2.4 Fluorescent microscopy 12 2.5 Yeast two-hybrid assay 13 2.6 Growth curve 13 2.7 Pull-down assay 14 2.8 Membrane protection assay 14 2.9 Subcellular fractionation 15 2.10 CPY sesecretory analysis 16 Chapter 3: Results 17 3.1 Atg20 is essential for the Cvt pathway but not general autophagy 17 3.2 Atg20 sequence analysis and structural modeling reveal a BAR domain in the C-terminus 19 3.3 The BAR domain of Atg20 is important for its function in the Cvt pathway 20 3.4 The BAR domain of Atg20 plays a crucial role in determining its own localization and the targeting of Atg24 to the PAS 23 3.5 The BAR domain of Atg20 mediates its interaction with Atg24 but not Atg11 and Atg17 24 3.6 Atg20 may interact with itself via AHL in an antiparallel manner 26 3.7 The last 49 residues of Atg20 are involved in proliferation 27 3.8 Point mutation in the amphipathic helix L disturbs the Cvt vesicle formation 27 3.9 The BAR domain of Atg20 is partially involved in Snc1 retrieval 29 3.10 Atg20 does not participate in the regulation of carboxylpeptidase Y (CPY) transport 30 3.11 Atg20 and Atg24 abundantly accumulate at the PAS in ymr1Δ cells 31 Chapter 4: Discussion 33 4.1 Atg20 may be involved in the general autophagy. 33 4.2 The BAR domain of Atg20 mediates the localization of Atg20 and Atg24 and regulates the Snc1 retrieval. 33 4.3 The protein-protein interaction region of Atg20 36 4.4 Atg20 may interact with itself via AHL in an antiparallel manner 36 4.5 Atg20 may play a role in the control of cell growth 37 4.6 Leu378 and Ile382 of amphipathic helix L are important for the Cvt vesicle formation. 37 4.7 Atg20 and Atg24 are released from the PAS after PI3P dephosphorylation. 38 References 40 Tables 49 Table 1. Yeast strains used in this study 49 Table 2. Primers used for plasmid construction 50 Table 3. Plasmids used in this study 51 Table 4. Comparison of functional domains of Atg20 54 Figures 55 Figure 1. Atg20 is required for the Cvt pathway but not for starvation-induced autophagy. 56 Figure 2. Modeling structure of Atg20. 58 Figure 3. The BAR domain of Atg20 is important for the Cvt pathway. 60 Figure 4. BAR domain of Atg20 is crucial for determining its own localization. 62 Figure 5. BAR domain of Atg20 is involved in the targeting of Atg24 to the PAS. 63 Figure 6. Atg20 may interact with Atg11 via multiple domains. 64 Figure 7. Atg20 may interact with Atg17 via multiple domains. 66 Figure 8. The last 49 residues of Atg20 mediate its interaction with Atg24. 69 Figure 9. Atg20 may interact with itself via AHL in an anti-parallel manner. 76 Figure 10. Atg20ΔC49 shows dominant-negative effects on proliferation. 78 Figure 11. Atg20L378EI382E disturbs the Cvt vesicle formation but still fractionates with vesicle membranes. 80 Figure 12. The BAR domain of Atg20 is partially involved in Snc1 retrieval in the endomembrane system. 81 Figure 13. Atg20 does not participate in carboxylpeptidase Y (CPY) transport. 83 Figure 14. Atg20 and Atg24 abundantly accumulates at the PAS in ymr1Δ cells. 85 Figure 15. The model of Atg20 participation in the Cvt pathway and its functional domains. 88 | |
| dc.language.iso | en | |
| dc.title | Atg20的功能性區域與其在細胞質至液胞傳遞途徑中的機制 | zh_TW |
| dc.title | Insight into Atg20: Its functional domains and the mechanism in the Cvt pathway | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 董桂書(Kuei-Shu Tung),羅凱尹(Kai-Yin Lo) | |
| dc.subject.keyword | 細胞自噬,細胞質至液胞傳遞途徑,Snc1回收,Atg20,BAR區域,雙極性螺旋,細胞質至液胞運輸小泡的形成, | zh_TW |
| dc.subject.keyword | autophagy,the Cvt pathway,Snc1 retrieval,Atg20,Bin/Amphiphysin/Rvs (BAR) domain,amphipathic helix,Cvt vesicle formation, | en |
| dc.relation.page | 88 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-15 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究所 | zh_TW |
| 顯示於系所單位： | 動物學研究所 | |
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