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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳光超(Guang-Chao Chen) | |
dc.contributor.author | Jung-Kun Wen | en |
dc.contributor.author | 溫榮崑 | zh_TW |
dc.date.accessioned | 2021-06-17T03:20:54Z | - |
dc.date.available | 2023-06-29 | |
dc.date.copyright | 2018-06-29 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-06-22 | |
dc.identifier.citation | Alers, S., Loffler, A.S., Wesselborg, S., and Stork, B. (2012). Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Molecular and cellular biology 32, 2-11.
Amcheslavsky, A., Ito, N., Jiang, J., and Ip, Y.T. (2011). Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells. The Journal of cell biology 193, 695-710. Andreatta, G., Kyriacou, C.P., Flatt, T., and Costa, R. (2018). Aminergic Signaling Controls Ovarian Dormancy in Drosophila. Scientific reports 8, 2030. Bader, C.A., Shandala, T., Ng, Y.S., Johnson, I.R., and Brooks, D.A. (2015). Atg9 is required for intraluminal vesicles in amphisomes and autolysosomes. Biology open 4, 1345-1355. Bai, H., Kang, P., and Tatar, M. (2012). Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain. Aging cell 11, 978-985. Berry, D.L., and Baehrecke, E.H. (2007). Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 131, 1137-1148. Bitto, A., Ito, T.K., Pineda, V.V., LeTexier, N.J., Huang, H.Z., Sutlief, E., Tung, H., Vizzini, N., Chen, B., Smith, K., et al. (2016). Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. eLife 5. Brand, A.H., and Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401-415. Budovskaya, Y.V., Stephan, J.S., Deminoff, S.J., and Herman, P.K. (2005). An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase. Proceedings of the National Academy of Sciences of the United States of America 102, 13933-13938. Budovskaya, Y.V., Stephan, J.S., Reggiori, F., Klionsky, D.J., and Herman, P.K. (2004). The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. The Journal of biological chemistry 279, 20663-20671. Burman, C., and Ktistakis, N.T. (2010). Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS letters 584, 1302-1312. Chan, C.C., Scoggin, S., Wang, D., Cherry, S., Dembo, T., Greenberg, B., Jin, E.J., Kuey, C., Lopez, A., Mehta, S.Q., et al. (2011). Systematic discovery of Rab GTPases with synaptic functions in Drosophila. Current biology : CB 21, 1704-1715. Chang, C.Y., and Huang, W.P. (2007). Atg19 mediates a dual interaction cargo sorting mechanism in selective autophagy. Mol Biol Cell 18, 919-929. Chen, G.C., Lee, J.Y., Tang, H.W., Debnath, J., Thomas, S.M., and Settleman, J. (2008). Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation. Autophagy 4, 37-45. Chen, S.F., Kang, M.L., Chen, Y.C., Tang, H.W., Huang, C.W., Li, W.H., Lin, C.P., Wang, C.Y., Wang, P.Y., Chen, G.C., et al. (2012). Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila. J Biomed Sci 19, 52. Cheong, H., Nair, U., Geng, J., and Klionsky, D.J. (2008). The Atg1 kinase complex is involved in the regulation of protein recruitment to initiate sequestering vesicle formation for nonspecific autophagy in Saccharomyces cerevisiae. Mol Biol Cell 19, 668-681. Choi, A.M., Ryter, S.W., and Levine, B. (2013). Autophagy in human health and disease. The New England journal of medicine 368, 651-662. Chong-Kopera, H., Inoki, K., Li, Y., Zhu, T., Garcia-Gonzalo, F.R., Rosa, J.L., and Guan, K.L. (2006). TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. The Journal of biological chemistry 281, 8313-8316. Codogno, P., and Meijer, A.J. (2010). Autophagy: a potential link between obesity and insulin resistance. Cell metabolism 11, 449-451. Cognigni, P., Bailey, A.P., and Miguel-Aliaga, I. (2011). Enteric neurons and systemic signals couple nutritional and reproductive status with intestinal homeostasis. Cell metabolism 13, 92-104. Colman, R.J., Anderson, R.M., Johnson, S.C., Kastman, E.K., Kosmatka, K.J., Beasley, T.M., Allison, D.B., Cruzen, C., Simmons, H.A., Kemnitz, J.W., et al. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201-204. de Kreutzenberg, S.V., Ceolotto, G., Papparella, I., Bortoluzzi, A., Semplicini, A., Dalla Man, C., Cobelli, C., Fadini, G.P., and Avogaro, A. (2010). Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes 59, 1006-1015. Decuypere, J.P., Monaco, G., Missiaen, L., De Smedt, H., Parys, J.B., and Bultynck, G. (2011). IP(3) Receptors, Mitochondria, and Ca Signaling: Implications for Aging. Journal of aging research 2011, 920178. 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. The Journal of cell biology 191, 155-168. Dibble, C.C., and Cantley, L.C. (2015). Regulation of mTORC1 by PI3K signaling. Trends in cell biology 25, 545-555. Drummond-Barbosa, D., and Spradling, A.C. (2001). Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Developmental biology 231, 265-278. Dunlop, E.A., Hunt, D.K., Acosta-Jaquez, H.A., Fingar, D.C., and Tee, A.R. (2011). ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding. Autophagy 7, 737-747. F, O.F., Rusten, T.E., and Stenmark, H. (2013). Phosphoinositide 3-kinases as accelerators and brakes of autophagy. The FEBS journal 280, 6322-6337. Feng, Y., He, D., Yao, Z., and Klionsky, D.J. (2014). The machinery of macroautophagy. Cell research 24, 24-41. Fimia, G.M., Di Bartolomeo, S., Piacentini, M., and Cecconi, F. (2011). Unleashing the Ambra1-Beclin 1 complex from dynein chains: Ulk1 sets Ambra1 free to induce autophagy. Autophagy 7, 115-117. Garelli, A., Gontijo, A.M., Miguela, V., Caparros, E., and Dominguez, M. (2012). Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579-582. Geng, J., and Klionsky, D.J. (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series. EMBO reports 9, 859-864. Gomez-Sanchez, R., Rose, J., Guimaraes, R., Mari, M., Papinski, D., Rieter, E., Geerts, W.J., Hardenberg, R., Kraft, C., Ungermann, C., et al. (2018). Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores. The Journal of cell biology. Goulas, S., Conder, R., and Knoblich, J.A. (2012). The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells. Cell stem cell 11, 529-540. Guo, S. (2014). Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. The Journal of endocrinology 220, T1-T23. Guo, Z., Lucchetta, E., Rafel, N., and Ohlstein, B. (2016). Maintenance of the adult Drosophila intestine: all roads lead to homeostasis. Current opinion in genetics & development 40, 81-86. Hamada, F.N., Rosenzweig, M., Kang, K., Pulver, S.R., Ghezzi, A., Jegla, T.J., and Garrity, P.A. (2008). An internal thermal sensor controlling temperature preference in Drosophila. Nature 454, 217-220. Haselton, A., Sharmin, E., Schrader, J., Sah, M., Poon, P., and Fridell, Y.W. (2010). Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance. Cell cycle 9, 3063-3071. Haselton, A.T., and Fridell, Y.W. (2010). Adult Drosophila melanogaster as a model for the study of glucose homeostasis. Aging 2, 523-526. He, C., and Klionsky, D.J. (2009). Regulation mechanisms and signaling pathways of autophagy. Annual review of genetics 43, 67-93. He, C., Song, H., Yorimitsu, T., Monastyrska, I., Yen, W.L., Legakis, J.E., and Klionsky, D.J. (2006). Recruitment of Atg9 to the preautophagosomal structure by Atg11 is essential for selective autophagy in budding yeast. The Journal of cell biology 175, 925-935. Heller, B., Adu-Gyamfi, E., Smith-Kinnaman, W., Babbey, C., Vora, M., Xue, Y., Bittman, R., Stahelin, R.V., and Wells, C.D. (2010). Amot recognizes a juxtanuclear endocytic recycling compartment via a novel lipid binding domain. The Journal of biological chemistry 285, 12308-12320. Hentze, J.L., Carlsson, M.A., Kondo, S., Nassel, D.R., and Rewitz, K.F. (2015). The Neuropeptide Allatostatin A Regulates Metabolism and Feeding Decisions in Drosophila. Scientific reports 5, 11680. Hu, J., Zacharek, S., He, Y.J., Lee, H., Shumway, S., Duronio, R.J., and Xiong, Y. (2008). WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes & development 22, 866-871. Imagawa, Y., Saitoh, T., and Tsujimoto, Y. (2016). Vital staining for cell death identifies Atg9a-dependent necrosis in developmental bone formation in mouse. Nature communications 7, 13391. Imai, K., Hao, F., Fujita, N., Tsuji, Y., Oe, Y., Araki, Y., Hamasaki, M., Noda, T., and Yoshimori, T. (2016). Atg9A trafficking through the recycling endosomes is required for autophagosome formation. Journal of cell science 129, 3781-3791. Inoki, K., Zhu, T., and Guan, K.L. (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590. Itakura, E., and Mizushima, N. (2010). Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy 6, 764-776. Jiang, H., and Edgar, B.A. (2012). Intestinal stem cell function in Drosophila and mice. Current opinion in genetics & development 22, 354-360. Jiang, H., Tian, A., and Jiang, J. (2016). Intestinal stem cell response to injury: lessons from Drosophila. Cellular and molecular life sciences : CMLS 73, 3337-3349. Jiang, P., and Mizushima, N. (2014). Autophagy and human diseases. Cell research 24, 69-79. Jorgensen, P., and Tyers, M. (2004). How cells coordinate growth and division. Current biology : CB 14, R1014-1027. Juhasz, G., Erdi, B., Sass, M., and Neufeld, T.P. (2007). Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes & development 21, 3061-3066. Jung, C.H., Seo, M., Otto, N.M., and Kim, D.H. (2011). ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy 7, 1212-1221. Kakuta, S., Yamamoto, H., Negishi, L., Kondo-Kakuta, C., Hayashi, N., and Ohsumi, Y. (2012). Atg9 vesicles recruit vesicle-tethering proteins Trs85 and Ypt1 to the autophagosome formation site. The Journal of biological chemistry 287, 44261-44269. Kannan, K., and Fridell, Y.W. (2013). Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction. Frontiers in physiology 4, 288. Kapuria, S., Karpac, J., Biteau, B., Hwangbo, D., and Jasper, H. (2012). Notch-mediated suppression of TSC2 expression regulates cell differentiation in the Drosophila intestinal stem cell lineage. PLoS genetics 8, e1003045. Katewa, S.D., and Kapahi, P. (2011). Role of TOR signaling in aging and related biological processes in Drosophila melanogaster. Experimental gerontology 46, 382-390. Kenyon, C.J. (2010). The genetics of ageing. Nature 464, 504-512. Kim, J., Kundu, M., Viollet, B., and Guan, K.L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology 13, 132-141. Kim, M., Park, H.L., Park, H.W., Ro, S.H., Nam, S.G., Reed, J.M., Guan, J.L., and Lee, J.H. (2013). Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging. Autophagy 9, 1201-1213. Klionsky, D.J. (2007). Autophagy: from phenomenology to molecular understanding in less than a decade. Nature reviews Molecular cell biology 8, 931-937. Komatsu, M., and Ichimura, Y. (2010). Physiological significance of selective degradation of p62 by autophagy. FEBS letters 584, 1374-1378. Kondo, S., and Ueda, R. (2013). Highly improved gene targeting by germline-specific Cas9 expression in Drosophila. Genetics 195, 715-721. Lamb, C.A., Nuhlen, S., Judith, D., Frith, D., Snijders, A.P., Behrends, C., and Tooze, S.A. (2016). TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic. The EMBO journal 35, 281-301. Laplante, M., and Sabatini, D.M. (2012). mTOR signaling in growth control and disease. Cell 149, 274-293. Lee, J.H., Budanov, A.V., Park, E.J., Birse, R., Kim, T.E., Perkins, G.A., Ocorr, K., Ellisman, M.H., Bodmer, R., Bier, E., et al. (2010). Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327, 1223-1228. Lee, J.S., Li, Q., Lee, J.Y., Lee, S.H., Jeong, J.H., Lee, H.R., Chang, H., Zhou, F.C., Gao, S.J., Liang, C., et al. (2009a). FLIP-mediated autophagy regulation in cell death control. Nature cell biology 11, 1355-1362. Lee, S.B., Kim, S., Lee, J., Park, J., Lee, G., Kim, Y., Kim, J.M., and Chung, J. (2007). ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase. EMBO reports 8, 360-365. Lee, W.C., Beebe, K., Sudmeier, L., and Micchelli, C.A. (2009b). Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation. Development 136, 2255-2264. Lemaitre, B., and Miguel-Aliaga, I. (2013). The digestive tract of Drosophila melanogaster. Annual review of genetics 47, 377-404. Levine, B., and Kroemer, G. (2008). Autophagy in the pathogenesis of disease. Cell 132, 27-42. Levine, B., Mizushima, N., and Virgin, H.W. (2011). Autophagy in immunity and inflammation. Nature 469, 323-335. Levine, B., and Yuan, J. (2005). Autophagy in cell death: an innocent convict? The Journal of clinical investigation 115, 2679-2688. Linneweber, G.A., Jacobson, J., Busch, K.E., Hudry, B., Christov, C.P., Dormann, D., Yuan, M., Otani, T., Knust, E., de Bono, M., et al. (2014). Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching. Cell 156, 69-83. Lipinski, M.M., Zheng, B., Lu, T., Yan, Z., Py, B.F., Ng, A., Xavier, R.J., Li, C., Yankner, B.A., Scherzer, C.R., et al. (2010). Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 107, 14164-14169. Liu, Y., Liao, S., Veenstra, J.A., and Nassel, D.R. (2016). Drosophila insulin-like peptide 1 (DILP1) is transiently expressed during non-feeding stages and reproductive dormancy. Scientific reports 6, 26620. Mari, M., Griffith, J., Rieter, E., Krishnappa, L., Klionsky, D.J., and Reggiori, F. (2010). An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis. The Journal of cell biology 190, 1005-1022. Martinez, V.G., Javadi, C.S., Ngo, E., Ngo, L., Lagow, R.D., and Zhang, B. (2007). Age-related changes in climbing behavior and neural circuit physiology in Drosophila. Developmental neurobiology 67, 778-791. Massey-Harroche, D., Delgrossi, M.H., Lane-Guermonprez, L., Arsanto, J.P., Borg, J.P., Billaud, M., and Le Bivic, A. (2007). Evidence for a molecular link between the tuberous sclerosis complex and the Crumbs complex. Human molecular genetics 16, 529-536. Mathew, R., Karp, C.M., Beaudoin, B., Vuong, N., Chen, G., Chen, H.Y., Bray, K., Reddy, A., Bhanot, G., Gelinas, C., et al. (2009). Autophagy suppresses tumorigenesis through elimination of p62. Cell 137, 1062-1075. McGuire, S.E., Mao, Z., and Davis, R.L. (2004). Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Science's STKE : signal transduction knowledge environment 2004, pl6. 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. Micchelli, C.A., and Perrimon, N. (2006). Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439, 475-479. Michel, D., Arsanto, J.P., Massey-Harroche, D., Beclin, C., Wijnholds, J., and Le Bivic, A. (2005). PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells. Journal of cell science 118, 4049-4057. Minois, N., Carmona-Gutierrez, D., Bauer, M.A., Rockenfeller, P., Eisenberg, T., Brandhorst, S., Sigrist, S.J., Kroemer, G., and Madeo, F. (2012). Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways. Cell death & disease 3, e401. Miron, M., and Sonenberg, N. (2001). Regulation of translation via TOR signaling: insights from Drosophila melanogaster. The Journal of nutrition 131, 2988S-2993S. Mizushima, N., and Levine, B. (2010). Autophagy in mammalian development and differentiation. Nature cell biology 12, 823-830. Mizushima, N., Levine, B., Cuervo, A.M., and Klionsky, D.J. (2008). Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075. Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., and Ohsumi, Y. (2004). In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15, 1101-1111. Muller, H.A. (2000). Genetic control of epithelial cell polarity: lessons from Drosophila. Developmental dynamics : an official publication of the American Association of Anatomists 218, 52-67. Nakae, J., Kido, Y., and Accili, D. (2001). Distinct and overlapping functions of insulin and IGF-I receptors. Endocrine reviews 22, 818-835. Nakai, A., Yamaguchi, O., Takeda, T., Higuchi, Y., Hikoso, S., Taniike, M., Omiya, S., Mizote, I., Matsumura, Y., Asahi, M., et al. (2007). The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nature medicine 13, 619-624. Nakatogawa, H. (2013). Two ubiquitin-like conjugation systems that mediate membrane formation during autophagy. Essays in biochemistry 55, 39-50. Nascimbeni, A.C., Codogno, P., and Morel, E. (2017). Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. The FEBS journal 284, 1267-1278. Ohlstein, B., and Spradling, A. (2006). The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439, 470-474. Oldham, S., and Hafen, E. (2003). Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends in cell biology 13, 79-85. Orsi, A., Razi, M., Dooley, H.C., Robinson, D., Weston, A.E., Collinson, L.M., and Tooze, S.A. (2012). Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell 23, 1860-1873. Papinski, D., Schuschnig, M., Reiter, W., Wilhelm, L., Barnes, C.A., Maiolica, A., Hansmann, I., Pfaffenwimmer, T., Kijanska, M., Stoffel, I., et al. (2014). Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase. Molecular cell 53, 471-483. Partridge, L., Alic, N., Bjedov, I., and Piper, M.D. (2011). Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Experimental gerontology 46, 376-381. Penalva, C., and Mirouse, V. (2012). Tissue-specific function of Patj in regulating the Crumbs complex and epithelial polarity. Development 139, 4549-4554. Piper, M.D., Skorupa, D., and Partridge, L. (2005). Diet, metabolism and lifespan in Drosophila. Experimental gerontology 40, 857-862. Popovic, D., and Dikic, I. (2014). TBC1D5 and the AP2 complex regulate ATG9 trafficking and initiation of autophagy. EMBO reports 15, 392-401. Puri, C., Renna, M., Bento, C.F., Moreau, K., and Rubinsztein, D.C. (2013). Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell 154, 1285-1299. Rao, Y., Perna, M.G., Hofmann, B., Beier, V., and Wollert, T. (2016). The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy. Nature communications 7, 10338. 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. Rera, M., Bahadorani, S., Cho, J., Koehler, C.L., Ulgherait, M., Hur, J.H., Ansari, W.S., Lo, T., Jr., Jones, D.L., and Walker, D.W. (2011). Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell metabolism 14, 623-634. Riahi, Y., Wikstrom, J.D., Bachar-Wikstrom, E., Polin, N., Zucker, H., Lee, M.S., Quan, W., Haataja, L., Liu, M., Arvan, P., et al. (2016). Autophagy is a major regulator of beta cell insulin homeostasis. Diabetologia 59, 1480-1491. Roh, M.H., Liu, C.J., Laurinec, S., and Margolis, B. (2002). The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions. The Journal of biological chemistry 277, 27501-27509. Rosner, M., Hanneder, M., Siegel, N., Valli, A., and Hengstschlager, M. (2008). The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners. Mutation research 658, 234-246. Rowland, A.F., Fazakerley, D.J., and James, D.E. (2011). Mapping insulin/GLUT4 circuitry. Traffic 12, 672-681. Russell, R.C., Fang, C., and Guan, K.L. (2011). An emerging role for TOR signaling in mammalian tissue and stem cell physiology. Development 138, 3343-3356. Russell, R.C., Tian, Y., Yuan, H., Park, H.W., Chang, Y.Y., Kim, J., Kim, H., Neufeld, T.P., Dillin, A., and Guan, K.L. (2013). ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nature cell biology 15, 741-750. Russell, R.C., Yuan, H.X., and Guan, K.L. (2014). Autophagy regulation by nutrient signaling. Cell research 24, 42-57. Saitoh, T., Fujita, N., Hayashi, T., Takahara, K., Satoh, T., Lee, H., Matsunaga, K., Kageyama, S., Omori, H., Noda, T., et al. (2009). Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proceedings of the National Academy of Sciences of the United States of America 106, 20842-20846. Saxton, R.A., and Sabatini, D.M. (2017). mTOR Signaling in Growth, Metabolism, and Disease. Cell 169, 361-371. Scott, R.C., Juhasz, G., and Neufeld, T.P. (2007). Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Current biology : CB 17, 1-11. Scott, R.C., Schuldiner, O., and Neufeld, T.P. (2004). Role and regulation of starvation-induced autophagy in the Drosophila fat body. Developmental cell 7, 167-178. Sekito, T., Kawamata, T., Ichikawa, R., Suzuki, K., and Ohsumi, Y. (2009). Atg17 recruits Atg9 to organize the pre-autophagosomal structure. Genes to cells : devoted to molecular & cellular mechanisms 14, 525-538. Sen, A., Nagy-Zsver-Vadas, Z., and Krahn, M.P. (2012). Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity. The Journal of cell biology 199, 685-698. Sen, A., Sun, R., and Krahn, M.P. (2015). Localization and Function of Pals1-associated Tight Junction Protein in Drosophila Is Regulated by Two Distinct Apical Complexes. The Journal of biological chemistry 290, 13224-13233. Shao, W., and Espenshade, P.J. (2012). Expanding roles for SREBP in metabolism. Cell metabolism 16, 414-419. Shim, J., Gururaja-Rao, S., and Banerjee, U. (2013). Nutritional regulation of stem and progenitor cells in Drosophila. Development 140, 4647-4656. 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. Nature cell biology 6, 1221-1228. Shimobayashi, M., and Hall, M.N. (2014). Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nature reviews Molecular cell biology 15, 155-162. Shin, K., Wang, Q., and Margolis, B. (2007). PATJ regulates directional migration of mammalian epithelial cells. EMBO reports 8, 158-164. Simonsen, A., Cumming, R.C., Brech, A., Isakson, P., Schubert, D.R., and Finley, K.D. (2008). Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4, 176-184. Suzuki, S.W., Yamamoto, H., Oikawa, Y., Kondo-Kakuta, C., Kimura, Y., Hirano, H., and Ohsumi, Y. (2015). Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation. Proceedings of the National Academy of Sciences of the United States of America 112, 3350-3355. 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. The Journal of cell biology 119, 301-311. Tang, H.W., Liao, H.M., Peng, W.H., Lin, H.R., Chen, C.H., and Chen, G.C. (2013). Atg9 interacts with dTRAF2/TRAF6 to regulate oxidative stress-induced JNK activation and autophagy induction. Developmental cell 27, 489-503. Tang, H.W., Wang, Y.B., Wang, S.L., Wu, M.H., Lin, S.Y., and Chen, G.C. (2011). Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy. The EMBO journal 30, 636-651. Tepass, U. (2012). The apical polarity protein network in Drosophila epithelial cells: regulation of polarity, junctions, morphogenesis, cell growth, and survival. Annual review of cell and developmental biology 28, 655-685. Tooze, S.A. (2010). The role of membrane proteins in mammalian autophagy. Seminars in cell & developmental biology 21, 677-682. Toth, M.L., Sigmond, T., Borsos, E., Barna, J., Erdelyi, P., Takacs-Vellai, K., Orosz, L., Kovacs, A.L., Csikos, G., Sass, M., et al. (2008). Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4, 330-338. Tsokanos, F.F., Albert, M.A., Demetriades, C., Spirohn, K., Boutros, M., and Teleman, A.A. (2016). eIF4A inactivates TORC1 in response to amino acid starvation. The EMBO journal 35, 1058-1076. Tsukada, M., and Ohsumi, Y. (1993). Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS letters 333, 169-174. Tucker, K.A., Reggiori, F., Dunn, W.A., Jr., and Klionsky, D.J. (2003). Atg23 is essential for the cytoplasm to vacuole targeting pathway and efficient autophagy but not pexophagy. The Journal of biological chemistry 278, 48445-48452. Twig, G., Elorza, A., Molina, A.J., Mohamed, H., Wikstrom, J.D., Walzer, G., Stiles, L., Haigh, S.E., Katz, S., Las, G., et al. (2008). Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. The EMBO journal 27, 433-446. Wang, T., Lao, U., and Edgar, B.A. (2009). TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. The Journal of cell biology 186, 703-711. Webber, J.L., and Tooze, S.A. (2010). Coordinated regulation of autophagy by p38alpha MAPK through mAtg9 and p38IP. The EMBO journal 29, 27-40. Wells, C.D., Fawcett, J.P., Traweger, A., Yamanaka, Y., Goudreault, M., Elder, K., Kulkarni, S., Gish, G., Virag, C., Lim, C., et al. (2006). A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 125, 535-548. Xiang, J., Bandura, J., Zhang, P., Jin, Y., Reuter, H., and Edgar, B.A. (2017). EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration. Nature communications 8, 15125. Xu, T., Nicolson, S., Denton, D., and Kumar, S. (2015). Distinct requirements of Autophagy-related genes in programmed cell death. Cell death and differentiation 22, 1792-1802. Yamamoto, H., Kakuta, S., Watanabe, T.M., Kitamura, A., Sekito, T., Kondo-Kakuta, C., Ichikawa, R., Kinjo, M., and Ohsumi, Y. (2012). Atg9 vesicles are an important membrane source during early steps of autophagosome formation. The Journal of cell biology 198, 219-233. Yamashita, Y.M., Fuller, M.T., and Jones, D.L. (2005). Signaling in stem cell niches: lessons from the Drosophila germline. Journal of cell science 118, 665-672. Yang, Z., and Klionsky, D.J. (2010). Eaten alive: a history of macroautophagy. Nature cell biology 12, 814-822. Yao, Z., Delorme-Axford, E., Backues, S.K., and Klionsky, D.J. (2015). Atg41/Icy2 regulates autophagosome formation. Autophagy 11, 2288-2299. 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. The Journal of cell biology 188, 101-114. Yoon, M.S., and Choi, C.S. (2016). The role of amino acid-induced mammalian target of rapamycin complex 1(mTORC1) signaling in insulin resistance. Experimental & molecular medicine 48, e201. Yorimitsu, T., and Klionsky, D.J. (2005). Autophagy: molecular machinery for self-eating. Cell death and differentiation 12 Suppl 2, 1542-1552. Young, A.R., Chan, E.Y., Hu, X.W., Kochl, R., Crawshaw, S.G., High, S., Hailey, D.W., Lippincott-Schwartz, J., and Tooze, S.A. (2006). Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. Journal of cell science 119, 3888-3900. 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. Zeng, X., Chauhan, C., and Hou, S.X. (2010). Characterization of midgut stem cell- and enteroblast-specific Gal4 lines in drosophila. Genesis 48, 607-611. Zeng, X., Chauhan, C., and Hou, S.X. (2013). Stem cells in the Drosophila digestive system. Advances in experimental medicine and biology 786, 63-78. Zhan, Y.P., Liu, L., and Zhu, Y. (2016). Taotie neurons regulate appetite in Drosophila. Nature communications 7, 13633. Zhang, H., Stallock, J.P., Ng, J.C., Reinhard, C., and Neufeld, T.P. (2000). Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes & development 14, 2712-2724. Zhou, C., Ma, K., Gao, R., Mu, C., Chen, L., Liu, Q., Luo, Q., Feng, D., Zhu, Y., and Chen, Q. (2017). Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell research 27, 184-201. Zhou, W., and Hong, Y. (2012). Drosophila Patj plays a supporting role in apical-basal polarity but is essential for viability. Development 139, 2891-2896. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69607 | - |
dc.description.abstract | 細胞自噬 (Autophagy)為細胞內高度保守的分解代謝機制,在各種壓力條件下,對於有機體存活,分化,發育,蛋白質質量控制,維持細胞穩態或病源體免疫反應來說,細胞自噬扮演重要的角色。而在調控細胞自噬反應的相關基因當中,細胞自噬相關基因9 (Atg9) 這一個具有多通道的穿膜蛋白,已往被認為是自噬體 (Autophagosomes)上膜的載體。根據之前的研究指出,Atg9能調節先天免疫反應以及氧化壓力條件下會調節JNK活性,這些研究都再再指出Atg9具有除了能夠調節細胞自噬外仍具有調控其他信息傳導路徑的功能。然而,Atg9在生物體發育過程中的分子調節及生理學上的重要性至今仍然不是非常的清楚。
在本研究中,我們透過Atg9的突變果蠅株,發現Atg9的缺乏會導致果蠅壽命縮短、活動力缺陷以及對於壓力的敏感性增加。除此之外,缺乏Atg9也造成果蠅腸道形態異常,腸道細胞明顯增大。有趣的是,我們發現抑制TOR信息傳導路徑可以回復Atg9突變果蠅的腸道細胞缺陷。進一步的我們找出Atg9透過與緊密連接蛋白(Patj)及TSC2的相互作用,進而調節TOR的活性。並且當缺乏Atg9時會導致TSC2蛋白質含量明顯降低。我們的研究結果揭示了Atg9和TOR信息傳導路徑在調控細胞生長和組織恆定性之間的拮抗關係。此外,我們透過遺傳操縱和系統性分析方法分析Atg9的突變果蠅株。我們發現Atg9的缺失也造成雌性果蠅具有生殖缺陷的現象。而在成蠅大腦中,Atg9高度表現在某些特定神經元區域。Atg9突變果蠅株所造成的生理現象以及在成蠅大腦神經元迴路上的表達模式,促使我們更進一步的想釐清Atg9在大腦神經元迴路中的功能以及如何調控全身性的代謝功能。 | zh_TW |
dc.description.abstract | Autophagy is a highly conserved lysosome-mediated catabolic process, which can be activated by nutrient deprivation or other environment stresses. Autophagy is essential for organism survival, differentiation, development, protein quality control, maintaining cellular homeostasis and pathogens immune response. Atg9 has been shown to be the only integral membrane protein and reputed as a potential membrane carrier of autophagosomes. Moreover, Atg9 have been found to modulate innate immune response and oxidative stress mediated c-Jun N-terminal kinase (JNK) activation, indicating that Atg9 has multiple role in regulation of autophagy and others pathways. However, the molecular regulation and physiological functions of Atg9 still remain to be explored.
In this thesis, we generated Atg9 null mutant flies and found that loss of Atg9 led to shortened lifespan, locomotor defects, and increased susceptibility to stress. Atg9 loss also resulted in aberrant adult midgut morphology with dramatically enlarged enterocytes. Interestingly, inhibiting the TOR signaling pathway rescued the midgut defects of the Atg9 mutants. In addition, Atg9 interacted with PALS1-associated tight junction protein (Patj), which associates with TSC2 to regulate TOR activity. Depletion of Atg9 caused a marked decrease in TSC2 levels. Our findings revealed an antagonistic relationship between Atg9 and TOR signaling in the regulation of cell growth and tissue homeostasis. Moreover, we discover that loss of Atg9 also causes female reproductive defects. In addition, Atg9 is highly expressed and enriched in some parts of fly brain. The Atg9 mutant phenotypes and the expression patterns, indicates that Atg9 may function in Drosophila adult brain neuron circuit and systemic metabolism. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T03:20:54Z (GMT). No. of bitstreams: 1 ntu-107-D01b48002-1.pdf: 6608231 bytes, checksum: 04e65ca0c4e8203027d1dc05ab62d963 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | Table of contents
Table of contents 3 中文摘要 5 Abstract 6 List of abbreviations 7 Chapter 1 General Introduction 8 1.1 Autophagy 8 1.1.1 The core machinery of autophagy 8 1.1.2 Regulation signaling pathway of autophagy 12 1.1.3 The physiological roles of autophagy 14 1.2 Atg9 19 1.2.1 General background of Atg9 19 1.2.2 Function of Atg9 in Autophagy 20 1.2.3 Other functions of Atg9 21 1.3 Insulin signaling pathway 22 1.3.1 Function of Insulin signaling pathway 22 1.3.2 Insulin signaling in Drosophila 23 Chapter 2 Results 25 2.1 Generation of Drosophila Atg9 mutant fly 25 2.2 Atg9 mutants have impaired autophagy and increased ubiquitination 26 2.3 Phenotype of Atg9 mutants 27 2.4 Atg9 is required for proper adult midgut morphogenesis 28 2.5 Atg9 acts in ECs to regulate cell growth 30 2.6 Functional interaction between Atg9 and the TOR pathway 32 2.7 Atg9 interacts with Patj and TSC2 to regulate midgut cell growth 34 2.8 Atg9 expression pattern in Drosophila brain 36 2.9 Atg9 regulate food intake behavior 38 2.10 Loss of Atg9 in brain extends lifespan 38 2.11 Loss of Atg9 caused female sterility and abnormal phenotype in ovarioles 39 Chapter 3 Discussion 41 Chapter 4 Materials and Methods 47 Chapter 5 Figures 54 Figure 1. Generation of mutations in Drosophila Atg9. 54 Figure 2. Atg9 mutants have impaired autophagy and increased ubiquitination. 55 Figure 3. The Atg9 mutant flies display shortened lifespan, locomotor defects and decreased stress tolerance. 56 Figure 4. Atg9 is required for adult Drosophila midgut morphogenesis. 57 Figure 5. Atg9 is required for adult Drosophila midgut morphogenesis. 58 Figure 6. Loss of Atg9 leads to enlarged enterocytes. 59 Figure 7. Components of Atg1 kinase complex are required for adult midgut epithelium homeostasis. 60 Figure 8. Loss of Atg9 enhances TOR activity in Drosophila adult midgut. 61 Figure 9. Atg9 genetically interacts with components of the TOR signaling pathway. 62 Figure 10. Atg9 interacts with Patj. 63 Figure 11. Atg9 interacts with Patj to regulate midgut cell growth. 64 Figure 12. Atg9 interacts with TSC2 to regulate midgut cell growth 65 Figure 14. Loss of intestinal integrity in aged Atg9 mutant flies. 67 Figure 15. Atg9 depletion in visceral muscle does not cause any observable defects in the midgut. 68 Figure 16. Atg9 depletion does not affect cell size of larval imaginal discs. 69 Figure 17. Depletion of Atg1, Atg13, or Atg17 in adult fly causes intestinal barrier dysfunction and shortened lifespan. 70 Figure 18. Temporal knockdown of Atg genes impairs autophagy. 71 Figure 19. Rapamycin treatment rescues the intestinal barrier dysfunction of Atg9 mutants. 72 Figure 20. Atg9 genetically interacts with components of the insulin receptor/phosphoinositide 3-kinase (InR/PI3K) signaling pathway. 73 Figure 21. Atg9 genetically interacts with Patj. 74 Figure 22. Atg9 interacts with Patj and TSC2. 75 Figure 23. Atg9 expression pattern in Drosophila brain (A). 76 Figure 24. Atg9 expression pattern in Drosophila brain (B). 77 Figure 25. 78 Figure 26. Depletion of Atg9 in brain caused lifespan extension. 79 Figure 27. Loss of Atg9 caused female sterility and abnormal phenotypes in ovarioles. 80 Figure 28. Atg9 mutants exhibit aberrant germarium phenotypes. 81 Figure 29. Nutrient variation cannot rescue germarium defects in Atg9 mutant. 82 Chapter 6 References 83 | |
dc.language.iso | en | |
dc.title | 探討Atg9的生理功能與分子調控機制 | zh_TW |
dc.title | Characterization of Atg9 molecular regulation and physiological functions | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 姚季光(Chi-Kuang Yao),詹智強(Chih-Chiang Chan),汪宏達(Horng-Dar Wang),傅在峰(Tsai-Feng Fu) | |
dc.subject.keyword | 細胞自噬,細胞自噬相關基因9, | zh_TW |
dc.subject.keyword | Autophagy,Atg9, | en |
dc.relation.page | 106 | |
dc.identifier.doi | 10.6342/NTU201801070 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-06-25 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 基因體與系統生物學學位學程 | zh_TW |
顯示於系所單位: | 基因體與系統生物學學位學程 |
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