Table of Contents Author Guidelines Submit a Manuscript
Journal of Lipids
Volume 2011 (2011), Article ID 498768, 9 pages
http://dx.doi.org/10.1155/2011/498768
Review Article

PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast

1Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 jo Nishi-6 chome, Kitaku, Sapporo 060-0812, Japan
2Integrated Research Institute, Tokyo Institute of Technology, 4259-S2-12 Nagatsuda-cho, Midoriku, Yokohama 226-8503, Japan

Received 29 October 2010; Accepted 4 December 2010

Academic Editor: Xian-Cheng Jiang

Copyright © 2011 Keisuke Obara and Yoshinori Ohsumi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. Hara, K. Nakamura, M. Matsui et al., “Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice,” Nature, vol. 441, no. 7095, pp. 885–889, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. M. Komatsu, S. Waguri, T. Chiba et al., “Loss of autophagy in the central nervous system causes neurodegeneration in mice,” Nature, vol. 441, no. 7095, pp. 880–884, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. I. Nakagawa, A. Amano, N. Mizushima et al., “Autophagy defends cells against invading group A Streptococcus,” Science, vol. 306, no. 5698, pp. 1037–1040, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. N. Mizushima, “Autophagy: process and function,” Genes and Development, vol. 21, no. 22, pp. 2861–2873, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. M. Baba, K. Takeshige, N. Baba, and Y. Ohsumi, “Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization,” Journal of Cell Biology, vol. 124, no. 6, pp. 903–913, 1994. View at Google Scholar · View at Scopus
  6. M. Baba, M. Osumi, and Y. Ohsumi, “Anaysis of the membrane structures involved in autophagy in yeast by freeze-replica method,” Cell Structure and Function, vol. 20, no. 6, pp. 465–471, 1995. View at Google Scholar · View at Scopus
  7. N. Mizushima, A. Yamamoto, M. Hatano et al., “Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells,” Journal of Cell Biology, vol. 152, no. 4, pp. 657–667, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Obara and Y. Ohsumi, “Key questions about membrane dynamics during autophagy,” Seikagaku, vol. 80, no. 3, pp. 215–223, 2008. View at Google Scholar
  9. M. Tsukada and Y. Ohsumi, “Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae,” FEBS Letters, vol. 333, no. 1-2, pp. 169–174, 1993. View at Publisher · View at Google Scholar
  10. M. Thumm, “Isolation of autophagocytosis mutants of Saccharomyces cerevisiae,” FEBS Letters, vol. 349, no. 2, pp. 275–280, 1994. View at Publisher · View at Google Scholar
  11. D. J. Klionsky, J. M. Cregg, W. A. Dunn et al., “A unified nomenclature for yeast autophagy-related genes,” Developmental Cell, vol. 5, no. 4, pp. 539–545, 2003. View at Publisher · View at Google Scholar
  12. H. Nakatogawa, K. Suzuki, Y. Kamada, and Y. Ohsumi, “Dynamics and diversity in autophagy mechanisms: lessons from yeast,” Nature Reviews Molecular Cell Biology, vol. 10, no. 7, pp. 458–467, 2009. View at Publisher · View at Google Scholar · View at PubMed
  13. Z. Yang and D. J. Klionsky, “An overview of the molecular mechanism of autophagy,” Current Topics in Microbiology and Immunology, vol. 335, pp. 1–32, 2009. View at Google Scholar
  14. T. Noda, J. Kim, W. P. Huang et al., “Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways,” Journal of Cell Biology, vol. 148, no. 3, pp. 465–479, 2000. View at Publisher · View at Google Scholar
  15. T. Kirisako, M. Baba, N. Ishihara et al., “Formation process of autophagosome is traced with Apg8/Aut7p in yeast,” Journal of Cell Biology, vol. 147, no. 2, pp. 435–446, 1999. View at Publisher · View at Google Scholar
  16. T. Kirisako, Y. Ichimura, H. Okada et al., “The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway,” Journal of Cell Biology, vol. 151, no. 2, pp. 263–275, 2000. View at Publisher · View at Google Scholar
  17. Y. Ichimura, T. Kirisako, T. Takao et al., “A ubiquitin-like system mediates protein lipidation,” Nature, vol. 408, no. 6811, pp. 488–492, 2000. View at Publisher · View at Google Scholar · View at PubMed
  18. Y. Kabeya, N. Mizushima, T. Ueno et al., “LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing,” The EMBO Journal, vol. 19, no. 21, pp. 5720–5728, 2000. View at Google Scholar
  19. P. V. Schu, K. Takegawa, M. J. Fry, J. H. Stack, M. D. Waterfield, and S. D. Emr, “Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting,” Science, vol. 259, no. 5104, pp. 88–91, 1993. View at Google Scholar
  20. J. H. Stack and S. D. Emr, “Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities,” Journal of Biological Chemistry, vol. 269, no. 50, pp. 31552–31562, 1994. View at Google Scholar
  21. J. S. Robinson, D. J. Klionsky, L. M. Banta, and S. D. Emr, “Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases,” Molecular and Cellular Biology, vol. 8, no. 11, pp. 4936–4948, 1988. View at Google Scholar
  22. A. Kihara, T. Noda, N. Ishihara, and Y. Ohsumi, “Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase y sorting in Saccharomyces cerevisiae,” Journal of Cell Biology, vol. 153, no. 3, pp. 519–530, 2001. View at Google Scholar
  23. K. Obara, T. Noda, K. Niimi, and Y. Ohsumi, “Transport of phosphatidylinositol 3-phosphate into the vacuole via autophagic membranes in Saccharomyces cerevisiae,” Genes to Cells, vol. 13, no. 6, pp. 537–547, 2008. View at Publisher · View at Google Scholar · View at PubMed
  24. S. Kametaka, T. Okano, M. Ohsumi, and Y. Ohsumi, “Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae,” Journal of Biological Chemistry, vol. 273, no. 35, pp. 22284–22291, 1998. View at Publisher · View at Google Scholar
  25. A. Petiot, E. Ogier-Denis, E. F. C. Blommaart, A. J. Meijer, and P. Codogno, “Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pa7thways that control macroautophagy in HT-29 cells,” Journal of Biological Chemistry, vol. 275, no. 2, pp. 992–998, 2000. View at Publisher · View at Google Scholar
  26. E. Itakura, C. Kishi, K. Inoue, and N. Mizushima, “Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG,” Molecular Biology of the Cell, vol. 19, no. 12, pp. 5360–5372, 2008. View at Publisher · View at Google Scholar · View at PubMed
  27. Q. Sun, W. Fan, K. Chen, X. Ding, S. Chen, and Q. Zhong, “Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 49, pp. 19211–19216, 2008. View at Publisher · View at Google Scholar · View at PubMed
  28. K. Matsunaga, T. Saitoh, K. Tabata et al., “Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages,” Nature Cell Biology, vol. 11, no. 4, pp. 385–396, 2009. View at Publisher · View at Google Scholar · View at PubMed
  29. Y. Zhong, Q. J. Wang, X. Li et al., “Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex,” Nature Cell Biology, vol. 11, no. 4, pp. 468–476, 2009. View at Publisher · View at Google Scholar · View at PubMed
  30. J. H. Stack, D. B. DeWald, K. Takegawa, and S. D. Emr, “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,” Journal of Cell Biology, vol. 129, no. 2, pp. 321–334, 1995. View at Google Scholar
  31. P. K. Herman, J. H. Stack, and S. D. Emr, “A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery,” The EMBO Journal, vol. 10, no. 13, pp. 4049–4060, 1991. View at Google Scholar
  32. B. Levine, S. Sinha, and G. Kroemer, “Bcl-2 family members: dual regulators of apoptosis and autophagy,” Autophagy, vol. 4, no. 5, pp. 600–606, 2008. View at Google Scholar
  33. K. Obara, T. Sekito, and Y. Ohsumi, “Assortment of phosphatidylinositol 3-kinase complexes-Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae,” Molecular Biology of the Cell, vol. 17, no. 4, pp. 1527–1539, 2006. View at Publisher · View at Google Scholar · View at PubMed
  34. K. Suzuki, T. Kirisako, Y. Kamada, N. Mizushima, T. Noda, and Y. Ohsumi, “The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation,” The EMBO Journal, vol. 20, no. 21, pp. 5971–5981, 2001. View at Publisher · View at Google Scholar · View at PubMed
  35. K. Suzuki, Y. Kubota, T. Sekito, and Y. Ohsumi, “Hierarchy of Atg proteins in pre-autophagosomal structure organization,” Genes to Cells, vol. 12, no. 2, pp. 209–218, 2007. View at Publisher · View at Google Scholar · View at PubMed
  36. D. J. Gillooly, I. C. Morrow, M. Lindsay et al., “Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells,” The EMBO Journal, vol. 19, no. 17, pp. 4577–4588, 2000. View at Google Scholar
  37. K. Obara and Y. Ohsumi, “Dynamics and function of PtdIns(3)P in autophagy,” Autophagy, vol. 4, no. 7, pp. 952–954, 2008. View at Google Scholar
  38. C. G. Burd and S. D. Emr, “Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains,” Molecular Cell, vol. 2, no. 1, pp. 157–162, 1998. View at Google Scholar
  39. J. W. Yu and M. A. Lemmon, “All phox homology (PX) domains from Saccharomyces cerevisiae specifically recognize phosphatidylinositol 3-phosphate,” Journal of Biological Chemistry, vol. 276, no. 47, pp. 44179–44184, 2001. View at Publisher · View at Google Scholar · View at PubMed
  40. D. C. Nice, T. K. Sato, P. E. Stromhaug, S. D. Emr, and D. J. Klionsky, “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,” Journal of Biological Chemistry, vol. 277, no. 33, pp. 30198–30207, 2002. View at Google Scholar
  41. D. J. Klionsky, R. Cueva, and D. S. Yaver, “Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway,” Journal of Cell Biology, vol. 119, no. 2, pp. 287–300, 1992. View at Publisher · View at Google Scholar
  42. T. M. Harding, K. A. Morano, S. V. Scott, and D. J. Klionsky, “Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway,” Journal of Cell Biology, vol. 131, no. 3, pp. 591–602, 1995. View at Publisher · View at Google Scholar
  43. P. E. Strømhaug, F. Reggiori, J. Guan, C. W. Wang, and D. J. Klionsky, “Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy,” Molecular Biology of the Cell, vol. 15, no. 8, pp. 3553–3566, 2004. View at Publisher · View at Google Scholar · View at PubMed
  44. S. K. Dove, R. C. Piper, R. K. McEwen et al., “Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors,” The EMBO Journal, vol. 23, no. 9, pp. 1922–1933, 2004. View at Publisher · View at Google Scholar · View at PubMed
  45. R. Krick, J. Tolstrup, A. Appelles, S. Henke, and M. Thumm, “The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy,” FEBS Letters, vol. 580, no. 19, pp. 4632–4638, 2006. View at Publisher · View at Google Scholar · View at PubMed
  46. H. Barth, K. Meiling-Wesse, U. D. Epple, and M. Thumm, “Mai1p is essential for maturation of proaminopeptidase I but not for autophagy,” FEBS Letters, vol. 512, no. 1–3, pp. 173–179, 2002. View at Publisher · View at Google Scholar
  47. J. A. Efe, R. J. Botelho, and S. D. Emr, “Atg18 regulates organelle morphology and Fab1 kinase activity independent of its membrane recruitment by phosphatidylinositol 3,5-bisphosphate,” Molecular Biology of the Cell, vol. 18, no. 11, pp. 4232–4244, 2007. View at Publisher · View at Google Scholar · View at PubMed
  48. K. Obara, T. Sekito, K. Niimi, and Y. Ohsumi, “The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function,” Journal of Biological Chemistry, vol. 283, no. 35, pp. 23972–23980, 2008. View at Publisher · View at Google Scholar · View at PubMed
  49. U. Nair, Y. Cao, Z. Xie, and D. J. Klionsky, “Roles of the lipid-binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole targeting pathway and autophagy,” Journal of Biological Chemistry, vol. 285, no. 15, pp. 11476–11488, 2010. View at Publisher · View at Google Scholar · View at PubMed
  50. T. Hanada, N. N. Noda, Y. Satomi et al., “The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy,” Journal of Biological Chemistry, vol. 282, no. 52, pp. 37298–37302, 2007. View at Publisher · View at Google Scholar · View at PubMed
  51. H. Nakatogawa, Y. Ichimura, and Y. Ohsumi, “Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion,” Cell, vol. 130, no. 1, pp. 165–178, 2007. View at Publisher · View at Google Scholar · View at PubMed
  52. Z. Xie, U. Nair, and D. J. Klionsky, “Atg8 controls phagophore expansion during autophagosome formation,” Molecular Biology of the Cell, vol. 19, no. 8, pp. 3290–3298, 2008. View at Publisher · View at Google Scholar · View at PubMed
  53. T. Noda, K. Matsunaga, N. Taguchi-Atarashi, and T. Yoshimori, “Regulation of membrane biogenesis in autophagy via PI3P dynamics,” Seminars in Cell and Developmental Biology, vol. 21, pp. 671–676, 2010. View at Publisher · View at Google Scholar · View at PubMed
  54. A. Simonsen and S. A. Tooze, “Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes,” Journal of Cell Biology, vol. 186, no. 6, pp. 773–782, 2009. View at Publisher · View at Google Scholar · View at PubMed
  55. W. J. Brown, D. B. DeWald, S. D. Emr, H. Plutner, and W. E. Balch, “Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells,” Journal of Cell Biology, vol. 130, no. 4, pp. 781–796, 1995. View at Publisher · View at Google Scholar
  56. H. W. Davidson, “Wortmannin causes mistargeting of procathepsin D. Evidence for the involvement of a phosphatidylinositol 3-kinase in vesicular transport to lysosomes,” Journal of Cell Biology, vol. 130, no. 4, pp. 797–805, 1995. View at Publisher · View at Google Scholar
  57. E. Itakura and N. Mizushima, “Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins,” Autophagy, vol. 6, no. 6, pp. 764–776, 2010. View at Publisher · View at Google Scholar
  58. T. Hara, A. Takamura, C. Kishi et al., “FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells,” Journal of Cell Biology, vol. 181, no. 3, pp. 497–510, 2008. View at Publisher · View at Google Scholar · View at PubMed
  59. E. L. Axe, S. A. Walker, M. Manifava et al., “Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum,” Journal of Cell Biology, vol. 182, no. 4, pp. 685–701, 2008. View at Publisher · View at Google Scholar · View at PubMed
  60. M. Hayashi-Nishino, N. Fujita, T. Noda, A. Yamaguchi, T. Yoshimori, and A. Yamamoto, “A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation,” Nature Cell Biology, vol. 11, no. 12, pp. 1433–1437, 2009. View at Google Scholar
  61. K. Matsunaga, E. Morita, T. Saitoh et al., “Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L,” Journal of Cell Biology, vol. 190, no. 4, pp. 511–521, 2010. View at Publisher · View at Google Scholar · View at PubMed
  62. H. E. J. Polson, J. de Lartigue, D. J. Rigden et al., “Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation,” Autophagy, vol. 6, no. 4, pp. 506–522, 2010. View at Google Scholar · View at Scopus
  63. G. M. Fimia, A. Stoykova, A. Romagnoli et al., “Ambra1 regulates autophagy and development of the nervous system,” Nature, vol. 447, no. 7148, pp. 1121–1125, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. I. Vergne, E. Roberts, R. A. Elmaoued et al., “Control of autophagy initiation by phosphoinositide 3-phosphatase jumpy,” The EMBO Journal, vol. 28, no. 15, pp. 2244–2258, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. N. Taguchi-Atarashi, M. Hamasaki, K. Matsunaga et al., “Modulation of local Ptdins3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy,” Traffic, vol. 11, no. 4, pp. 468–478, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus