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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃偉邦 | |
dc.contributor.author | Nai-Yu Cheng | en |
dc.contributor.author | 鄭乃彧 | zh_TW |
dc.date.accessioned | 2021-06-15T06:43:16Z | - |
dc.date.available | 2011-07-25 | |
dc.date.copyright | 2011-07-25 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-06 | |
dc.identifier.citation | Abeliovich, H., Darsow, T., and Emr, S.D. (1999). Cytoplasm to vacuole trafficking of aminopeptidase I requires a t-SNARE-Sec1p complex composed of Tlg2p and Vps45p. EMBO J 18, 6005-6016.
Ano, Y., Hattori, T., Oku, M., Mukaiyama, H., Baba, M., Ohsumi, Y., Kato, N., and Sakai, Y. (2005). A sorting nexin PpAtg24 regulates vacuolar membrane dynamics during pexophagy via binding to phosphatidylinositol-3-phosphate. Mol Biol Cell 16, 446-457. 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. Bjorkoy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Overvatn, A., Stenmark, H., and Johansen, T. (2005). p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171, 603-614. 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. Carrera, A.C. (2004). TOR signaling in mammals. J Cell Sci 117, 4615-4616. Cebollero, E., and Reggiori, F. (2009). Regulation of autophagy in yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1793, 1413-1421. Chang, Y.Y., and Neufeld, T.P. (2009). An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell 20, 2004-2014. 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. 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. Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E.D., Sevier, C.S., Ding, H., Koh, J.L., Toufighi, K., Mostafavi, S., et al. (2010). The genetic landscape of a cell. Science 327, 425-431. Cullen, P.J. (2008). Endosomal sorting and signalling: an emerging role for sorting nexins. Nature Reviews Molecular Cell Biology 9, 574-582. De Duve, C., Pressman, B.C., Gianetto, R., Wattiaux, R., and Appelmans, F. (1955). Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J 60, 604-617. De Duve, C., and Wattiaux, R. (1966). Functions of lysosomes. Annu Rev Physiol 28, 435-492. Deretic, V., Singh, S., Master, S., Harris, J., Roberts, E., Kyei, G., Davis, A., de Haro, S., Naylor, J., Lee, H.H., et al. (2006). Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism. Cell Microbiol 8, 719-727. Di Bartolomeo, S., Corazzari, M., Nazio, F., Oliverio, S., Lisi, G., Antonioli, M., Pagliarini, V., Matteoni, S., Fuoco, C., Giunta, L., et al. (2010). The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J Cell Biol 191, 155-168. Dice, J.F. (2007). Chaperone-mediated autophagy. Autophagy 3, 295-299. Doelling, J.H., Walker, J.M., Friedman, E.M., Thompson, A.R., and Vierstra, R.D. (2002). The APG8/12-activating enzyme APG7 is required for proper nutrient recycling and senescence in Arabidopsis thaliana. J Biol Chem 277, 33105-33114. Geng, J.F., and Klionsky, D.J. (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. Embo Reports 9, 859-864. George, M.D., Baba, M., Scott, S.V., Mizushima, N., Garrison, B.S., Ohsumi, Y., and Klionsky, D.J. (2000). Apg5p functions in the sequestration step in the cytoplasm-to-vacuole targeting and macroautophagy pathways. Mol Biol Cell 11, 969-982. Guan, J., Stromhaug, P.E., George, M.D., Habibzadegah-Tari, P., Bevan, A., Dunn, W.A., Jr., and Klionsky, D.J. (2001). Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris. Mol Biol Cell 12, 3821-3838. 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. 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. 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. 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. Kamada, Y., Funakoshi, T., Shintani, T., Nagano, K., Ohsumi, M., and Ohsumi, Y. (2000). Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150, 1507-1513. Kamada, Y., Yoshino, K., Kondo, C., Kawamata, T., Oshiro, N., Yonezawa, K., and Ohsumi, Y. (2010). Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol Cell Biol 30, 1049-1058. Kanki, T., and Klionsky, D.J. (2008). Mitophagy in yeast occurs through a selective mechanism. J Biol Chem 283, 32386-32393. Kerr, J.F., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26, 239-257. Kim, I., 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., 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. Kirkin, V., Lamark, T., Johansen, T., and Dikic, I. (2009). NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets. Autophagy 5, 732-733. Klionsky, D.J. (2005). The molecular machinery of autophagy: unanswered questions. J Cell Sci 118, 7-18. 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. 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. Lee, H.K., Mattei, L.M., Steinberg, B.E., Alberts, P., Lee, Y.H., Chervonsky, A., Mizushima, N., Grinstein, S., and Iwasaki, A. (2010). In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 32, 227-239. Levine, B., and Deretic, V. (2007). Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7, 767-777. Levine, B., and Klionsky, D.J. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6, 463-477. 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. Lynch-Day, M.A., Bhandari, D., Menon, S., Huang, J., Cai, H., Bartholomew, C.R., Brumell, J.H., Ferro-Novick, S., and Klionsky, D.J. (2010). Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy. Proc Natl Acad Sci U S A 107, 7811-7816. Madeo, F., Eisenberg, T., and Kroemer, G. (2009). Autophagy for the avoidance of neurodegeneration. Genes Dev 23, 2253-2259. Meiling-Wesse, K., Barth, H., Voss, C., Eskelinen, E.L., Epple, U.D., and Thumm, M. (2004). Atg21 is required for effective recruitment of Atg8 to the preautophagosomal structure during the Cvt pathway. J Biol Chem 279, 37741-37750. Meiling-Wesse, K., Epple, U.D., Krick, R., Barth, H., Appelles, A., Voss, C., Eskelinen, E.L., and Thumm, M. (2005). Trs85 (Gsg1), a component of the TRAPP complexes, is required for the organization of the preautophagosomal structure during selective autophagy via the Cvt pathway. J Biol Chem 280, 33669-33678. Melendez, A., Talloczy, Z., Seaman, M., Eskelinen, E.L., Hall, D.H., and Levine, B. (2003). Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387-1391. Metcalf, D.J., Garcia-Arencibia, M., Hochfeld, W.E., and Rubinsztein, D.C. (2010). Autophagy and misfolded proteins in neurodegeneration. Exp Neurol. Nazarko, T.Y., Huang, J., Nicaud, J.M., Klionsky, D.J., and Sibirny, A.A. (2005). Trs85 is required for macroautophagy, pexophagy and cytoplasm to vacuole targeting in Yarrowia lipolytica and Saccharomyces cerevisiae. Autophagy 1, 37-45. Nedjic, J., Aichinger, M., Emmerich, J., Mizushima, N., and Klein, L. (2008). Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455, 396-400. 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. Noda, T., Kim, J., Huang, W.P., Baba, M., Tokunaga, C., Ohsumi, Y., and Klionsky, D.J. (2000). Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. J Cell Biol 148, 465-480. Noda, T., and Ohsumi, Y. (1998). Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273, 3963-3966. Obara, K., Sekito, T., Niimi, K., and Ohsumi, Y. (2008). The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. Journal of Biological Chemistry 283, 23972-23980. Ogawa, M., Yoshimori, T., Suzuki, T., Sagara, H., Mizushima, N., and Sasakawa, C. (2005). Escape of intracellular Shigella from autophagy. Science 307, 727-731. Ohashi, Y., and Munro, S. (2010). Membrane delivery to the yeast autophagosome from the Golgi-endosomal system. Mol Biol Cell 21, 3998-4008. 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. Paludan, C., Schmid, D., Landthaler, M., Vockerodt, M., Kube, D., Tuschl, T., and Munz, C. (2005). Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307, 593-596. Pankiv, S., Clausen, T.H., Lamark, T., Brech, A., Bruun, J.A., Outzen, H., Overvatn, A., Bjorkoy, G., and Johansen, T. (2007). p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282, 24131-24145. Price, A., Seals, D., Wickner, W., and Ungermann, C. (2000). The docking stage of yeast vacuole fusion requires the transfer of proteins from a cis-SNARE complex to a Rab/Ypt protein. J Cell Biol 148, 1231-1238. Reggiori, F., Monastyrska, I., Shintani, T., and Klionsky, D.J. (2005). The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae. Mol Biol Cell 16, 5843-5856. Reggiori, F., Tucker, K.A., Stromhaug, P.E., and Klionsky, D.J. (2004). The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Developmental Cell 6, 79-90. Reggiori, F., Wang, C.W., Stromhaug, P.E., Shintani, T., and Klionsky, D.J. (2003). Vps51 is part of the yeast Vps fifty-three tethering complex essential for retrograde traffic from the early endosome and Cvt vesicle completion. J Biol Chem 278, 5009-5020. Robinson, J.S., Klionsky, D.J., Banta, L.M., and Emr, S.D. (1988). Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol 8, 4936-4948. Rosenfeldt, M.T., and Ryan, K.M. (2011). The multiple roles of autophagy in cancer. Carcinogenesis. Saftig, P., and Klumperman, J. (2009). Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 10, 623-635. 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. Sato, T.K., Rehling, P., Peterson, M.R., and Emr, S.D. (2000). Class C Vps protein complex regulates vacuolar SNARE pairing and is required for vesicle docking/fusion. Mol Cell 6, 661-671. Schmid, D., and Munz, C. (2007). Innate and adaptive immunity through autophagy. Immunity 27, 11-21. 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. Scott, S.V., Nice, D.C., 3rd, Nau, J.J., Weisman, L.S., Kamada, Y., Keizer-Gunnink, I., Funakoshi, T., Veenhuis, M., Ohsumi, Y., and Klionsky, D.J. (2000). Apg13p and Vac8p are part of a complex of phosphoproteins that are required for cytoplasm to vacuole targeting. J Biol Chem 275, 25840-25849. Seaman, M.N.J. (2008). Endosome protein sorting: motifs and machinery. Cellular and Molecular Life Sciences 65, 2842-2858. 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. 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. Skanland, S.S., Walchli, S., Brech, A., and Sandvig, K. (2009). SNX4 in complex with clathrin and dynein: implications for endosome movement. PLoS One 4, e5935. Smith, R.D., and Lupashin, V.V. (2008). Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation. Carbohydr Res 343, 2024-2031. Stromhaug, P.E., Reggiori, F., Guan, J., Wang, C.W., and Klionsky, D.J. (2004). Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol Biol Cell 15, 3553-3566. 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. Teasdale, R.D., Loci, D., Houghton, F., Karlsson, L., and Gleeson, P.A. (2001). A large family of endosome-localized proteins related to sorting nexin 1. Biochem J 358, 7-16. Teter, S.A., Eggerton, K.P., Scott, S.V., Kim, J., Fischer, A.M., and Klionsky, D.J. (2001). Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem 276, 2083-2087. Traer, C.J., Rutherford, A.C., Palmer, K.J., Wassmer, T., Oakley, J., Attar, N., Carlton, J.G., Kremerskothen, J., Stephens, D.J., and Cullen, P.J. (2007). SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment. Nat Cell Biol 9, 1370-1380. 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. Ungar, D., Oka, T., Krieger, M., and Hughson, F.M. (2006). Retrograde transport on the COG railway. Trends Cell Biol 16, 113-120. van Weering, J.R.T., Verkade, P., and Cullen, P.J. (2010). SNX-BAR proteins in phosphoinositide-mediated, tubular-based endosomal sorting. Seminars in Cell and Developmental Biology 21, 371-380. 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. Wang, Z., Wilson, W.A., Fujino, M.A., and Roach, P.J. (2001b). Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol Cell Biol 21, 5742-5752. Winslow, A.R., and Rubinsztein, D.C. (2008). Autophagy in neurodegeneration and development. Biochim Biophys Acta 1782, 723-729. Wurmser, A.E., and Emr, S.D. (1998). Phosphoinositide signaling and turnover: PtdIns(3)P, a regulator of membrane traffic, is transported to the vacuole and degraded by a process that requires lumenal vacuolar hydrolase activities. EMBO J 17, 4930-4942. Wurmser, A.E., Sato, T.K., and 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, 551-562. Xu, Y., and Eissa, N.T. (2010). Autophagy in innate and adaptive immunity. Proc Am Thorac Soc 7, 22-28. 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. Yen, W.L., Legakis, J.E., Nair, U., and Klionsky, D.J. (2007). Atg27 is required for autophagy-dependent cycling of Atg9. Mol Biol Cell 18, 581-593. Yen, W.L., Shintani, T., Nair, U., Cao, Y., Richardson, B.C., Li, Z., Hughson, F.M., Baba, M., and Klionsky, D.J. (2010). The conserved oligomeric Golgi complex is involved in double-membrane vesicle formation during autophagy. J Cell Biol 188, 101-114. 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. Yorimitsu, T., Zaman, S., Broach, J.R., and Klionsky, D.J. (2007). Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae. Mol Biol Cell 18, 4180-4189. 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. Zhong, Q., Lazar, C.S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S.D., and Gill, G.N. (2002). Endosomal localization and function of sorting nexin 1. Proc Natl Acad Sci U S A 99, 6767-6772. Zhong, Q., Watson, M.J., Lazar, C.S., Hounslow, A.M., Waltho, J.P., and Gill, G.N. (2005). Determinants of the endosomal localization of sorting nexin 1. Mol Biol Cell 16, 2049-2057. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47941 | - |
dc.description.abstract | 細胞自噬(autophagy)是普遍存在所有真核生物的一種分解機制。當細胞處於壓力環境,特別是營養缺乏狀況,細胞自噬的活性會上升,誘導雙層膜構造形成,將周遭的物質非選擇性地包裹起來,此種雙層膜狀囊胞稱為自噬體(autophagosome)。自噬體最後會與液胞融合而分解內容物質,所釋出的小分子單體可供重新利用,維持細胞在惡劣環境中的生理恆定。細胞自噬也可以選擇性地移除過量或受損胞器,像是過氧化物酶體自噬(pexophagy)和粒線體自噬(mitophagy)。在出芽酵母菌(Saccharomyces cerevisiae)中,細胞質至液胞傳遞途徑(cytoplasm-to-vacuole targeting pathway, Cvt pathway)是一種特殊的選擇性細胞自噬,當細胞處於養分充足的生理環境時,細胞質至液胞傳遞途徑仍維持低度活性,持續運送液胞水解酶aminopeptidase I前驅物(prApeI)及α-mannosidase I (AmsI)。細胞質至液胞傳遞途徑和非選擇性細胞自噬共享許多核心調節分子,然而,細胞質至液胞傳遞途徑也需要特殊的調節蛋白參與,例如Atg24蛋白質。
Atg24是一個具有PI3P分子結合能力的蛋白質;它參與選擇性細胞自噬的調控,但並非養分缺乏引發之細胞自噬所必需。此外,Atg24也參與在內膜系統的蛋白質運輸途徑當中。本篇研究發現,Atg24調控在細胞質至液胞傳遞途徑之囊胞形成步驟。Atg24運送至囊胞形成位置(pre-autophagosomal structure, PAS)受到PI3K複合體I、Atg20和Trs85的調節。進一步分析Atg24蛋白質結構發現,Atg24的羰基端具有兩個螺旋結構(coiled-coil domain):其中第一螺旋結構是選擇性細胞自噬所必需,而兩個螺旋結構都參與Snc1蛋白質在內膜系統的回收機制當中。然而,第一螺旋結構並不負責Atg24與已知的結合蛋白Atg17和Atg20之交互作用,卻藉由未知的機制調控Atg24本身以及Atg20在細胞質內的分布。由本文的研究結果顯示:在細胞質至液胞傳遞途徑的過程中,Atg24-Atg20複合體移動到囊胞形成位置,隨後Atg24和Atg20再共同調控雙層膜囊胞的形成。然而,Atg24如何與細胞自噬的核心調控分子合作完成選擇性細胞自噬的過程,有待更進一步的研究了解。 | zh_TW |
dc.description.abstract | Autophagy is a highly conserved degradation pathway among all eukaryotes that can be induced under stress conditions, such as starvation. During the process, portions of cytoplasm are non-selectively engulfed into double-membrane vesicles called autophagosomes and subsequently delivered to the vacuole for degradation. The small molecules released from the process can be used to maintain cellular homeostasis. However, the degradation processes can occur selectively to remove excess or damaged organelles, for example, pexophagy and mitophagy. In the budding yeast Saccharomyces cerevisiae, the cytoplasm-to-vacuole targeting (Cvt) pathway is a unique type of selective autophagy that is constitutively active in growth condition for biosynthetic transport of vacuolar enzymes, such as precursors of aminopeptidase I and α-mannosidase. Although the Cvt pathway shares the same core machinery with bulk autophagy, it also requires specific regulatory proteins. In this study, I used the Cvt pathway as a model for analyzing the regulatory mechanisms underlying selective autophagy and investigated the role of selective autophagy-specific regulatory protein Atg24.
Atg24 is a PI3P-binding protein essential for selective autophagy but not bulk autophagy. Moreover, Atg24 is also involved in the endosome-to-Golgi protein traffic. I found that Atg24 participates in the vesicle formation step of the Cvt pathway and its recruitment to the PAS (pre-autophagosomal structure) is regulated by the PI3K complex I, Atg20 and Trs85. Besides, Atg24 contains two coiled-coil domains at the C terminus. Only the coiled-coil domain 1 is necessary for selective autophagy, whereas both two coiled-coil domains are required for retrieval of Snc1 in endomembrane trafficking. Although the coiled-coil domain 1 of Atg24 does not mediate its association with known interaction partners Atg17 and Atg20, it determines the subcellular localization of itself as well as Atg20. Our data suggested that during the Cvt pathway, the Atg24-Atg20 complex appears at the PAS in a mutually dependent manner and together they directly assist the Cvt vesicle formation. Future studies are needed to characterize how Atg24 cooperates with the core autophagic machinery in details. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:43:16Z (GMT). No. of bitstreams: 1 ntu-100-R98b41003-1.pdf: 4918317 bytes, checksum: fc657b5c06449fa0c1a82ca1aa8df8b5 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 iii Abstract iv Chapter 1: Introduction 1 1.1 Overview of autophagy 1 1.2 The role of autophagy in cells 3 1.3 The molecular mechanism of autophagy 5 1.4 The selectivity of autophagy 6 1.5 The differences between the Cvt pathway and bulk autophagy 8 1.6 The role of Atg24 in the endomembrane traffic and the Cvt pathway 9 Chapter 2: Materials and Methods 12 2.1 Strains and media 12 2.2 Plasmids construction 12 2.3 Yeast two-hybrid assay 13 2.4 Fluorescence microscopy 13 2.5 Pull-down assay 14 2.6 Assays for pexophagy activity 14 2.7 Protease protection assay 15 2.8 Preparation of whole cell extracts for immunoblot analysis 16 Chapter 3: Results 17 3.1 Atg24 participates in the Cvt vesicle formation 17 3.2 Early-action Atg proteins accumulate at the PAS in atg24Δ cells 19 3.3 Atg24 is not involved in the recruitment of the late-action Atg proteins 21 3.4 The coiled-coil domain 1 of Atg24 is important for its function in the Cvt pathway 22 3.5 The coiled-coil domain 1 of Atg24 plays a crucial role in determining its own localization 23 3.6 The two coiled-coil domains of Atg24 do not mediate its interaction with the known autophagic partners, Atg17 and Atg20 24 3.7 Atg24 modulates the localization of Atg20 at the PAS and the endosomal compartments 25 3.8 Atg14, Atg20 and Trs85 are important for recruitment of Atg24 to the PAS 26 3.9 The two coiled-coil domains of Atg24 are involved in Snc1 retrieval in the endomembrane system 28 3.10 The coiled-coil domain 1 of Atg24 plays a role in pexophagy 29 Chapter 4: Discussion 31 4.1 Atg24 functions in the membrane expansion or vesicle completion step of the Cvt vesicle formation 31 4.2 The Cvt pathway defects in atg24Δ strains are not due to the disruption of the endosome-to-Golgi protein trafficking pathway 32 4.3 Atg24 plays a similar role in the Cvt pathway and pexophagy 33 4.4 Atg20 and Atg24 are mutually dependent for their PAS localization, but Atg24 plays a major role in their targeting to the endosomal compartments 35 4.5 Prospects 36 References 42 Tables 52 Figures. 56 | |
dc.language.iso | en | |
dc.title | 探討Atg24在出芽酵母菌細胞自噬調控上所扮演的角色 | zh_TW |
dc.title | Characterization of the role of Atg24 in autophagy regulation in Saccharomyces cerevisiae | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 羅凱尹,李心予,董桂書 | |
dc.subject.keyword | 細胞自噬,細胞質至液胞傳遞途徑,過氧化物酶,體自噬,Atg24, | zh_TW |
dc.subject.keyword | autophagy,the Cvt pathway,pexophagy,Atg24,Snc1 retrieval, | en |
dc.relation.page | 81 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-07-06 | |
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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