DOI QR코드

DOI QR Code

The Roles of the SNARE Protein Sed5 in Autophagy in Saccharomyces cerevisiae

  • Zou, Shenshen (College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University) ;
  • Sun, Dan (College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University) ;
  • Liang, Yongheng (College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University)
  • 투고 : 2017.02.23
  • 심사 : 2017.07.19
  • 발행 : 2017.09.30

초록

Autophagy is a degradation pathway in eukaryotic cells in which aging proteins and organelles are sequestered into double-membrane vesicles, termed autophagosomes, which fuse with vacuoles to hydrolyze cargo. The key step in autophagy is the formation of autophagosomes, which requires different kinds of vesicles, including COPII vesicles and Atg9-containing vesicles, to transport lipid double-membranes to the phagophore assembly site (PAS). In yeast, the cis-Golgi localized t-SNARE protein Sed5 plays a role in endoplasmic reticulum (ER)-Golgi and intra-Golgi vesicular transport. We report that during autophagy, sed5-1 mutant cells could not properly transport Atg8 to the PAS, resulting in multiple Atg8 dots being dispersed into the cytoplasm. Some dots were trapped in the Golgi apparatus. Sed5 regulates the anterograde trafficking of Atg9-containing vesicles to the PAS by participating in the localization of Atg23 and Atg27 to the Golgi apparatus. Furthermore, we found that overexpression of SFT1 or SFT2 (suppressor of sed5 ts) rescued the autophagy defects in sed5-1 mutant cells. Our data suggest that Sed5 plays a novel role in autophagy, by regulating the formation of Atg9-containing vesicles in the Golgi apparatus, and the genetic interaction between Sft1/2 and Sed5 is essential for autophagy.

키워드

참고문헌

  1. Baba, M., Osumi, M., Scott, S.V., Klionsky, D.J., and Ohsumi, Y. (1997). Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome. J. Cell Biol. 139, 1687-1695. https://doi.org/10.1083/jcb.139.7.1687
  2. Backues, S.K., Orban, D.P., Bernard, A., Singh, K., Cao, Y., and Klionsky, D.J. (2015). Atg23 and Atg27 act at the early stages of Atg9 trafficking in S. cerevisiae. Traffic 16, 172-190. https://doi.org/10.1111/tra.12240
  3. Banfield, D.K., Lewis, M.J., and Pelham, H.R. (1995). A SNARE-like protein required for traffic through the Golgi complex. Nature 375, 806-809. https://doi.org/10.1038/375806a0
  4. Barlowe, C., Orci, L., Yeung, T., Hosobuchi, M., Hamamoto, S., Salama, N., Rexach, M. F., Ravazzola, M., Amherdt, M. and Schekman, R. (1994). COPII, a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum. Cell 77, 895-907. https://doi.org/10.1016/0092-8674(94)90138-4
  5. Cai, H., Yu, S., Menon, S., Cai, Y., Lazarova, D., Fu, C., Reinisch, K., Hay, J. C. and Ferro-Novick, S. (2007). TRAPPI tethers COPII vesicles by binding the coat subunit Sec23. Nature 445, 941-944. https://doi.org/10.1038/nature05527
  6. Conchon, S., Cao, X., Barlowe, C., and Pelham, H.R. (1999). Got1p and Sft2p, membrane proteins involved in traffic to the Golgi complex. EMBO J. 18, 3934-3946. https://doi.org/10.1093/emboj/18.14.3934
  7. Davis, S., and Ferro-Novick, S. (2015). Ypt1 and COPII vesicles act in autophagosome biogenesis and the early secretory pathway. Biochem. Soc. Trans. 43, 92-96. https://doi.org/10.1042/BST20140247
  8. Feng, Y., He, D., Yao, Z., and Klionsky, D.J. (2014). The machinery of macroautophagy. Cell Res. 24, 24-41. https://doi.org/10.1038/cr.2013.168
  9. Geng, J., and Klionsky, D.J. (2008). The Atg8 and Atg12 ubiquitinlike conjugation systems in macroautophagy. 'Protein modifications, beyond the usual suspects' review series. EMBO Rep. 9, 859-864. https://doi.org/10.1038/embor.2008.163
  10. Geng, J., and Klionsky, D.J. (2010). The Golgi as a potential membrane source for autophagy. Autophagy 6, 950-951. https://doi.org/10.4161/auto.6.7.13009
  11. Geng, J., Nair, U., Yasumura-Yorimitsu, K., and Klionsky, D.J. (2010). Post-Golgi Sec proteins are required for autophagy in Saccharomyces cerevisiae. Mol. Biol. Cell 21, 2257-2269. https://doi.org/10.1091/mbc.E09-11-0969
  12. Gietz, D., St Jean, A., Woods, R.A., and Schiestl, R.H. (1992). Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 20, 1425. https://doi.org/10.1093/nar/20.6.1425
  13. Graef, M., Friedman, J.R., Graham, C., Babu, M., and Nunnari, J. (2013). ER exit sites are physical and functional core autophagosome biogenesis components. Mol. Biol. Cell 24, 2918-2931. https://doi.org/10.1091/mbc.E13-07-0381
  14. Hailey, D.W., Rambold, A.S., Satpute-Krishnan, P., Mitra, K., Sougrat, R., Kim, P.K. and Lippincott-Schwartz, J. (2010). Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656-667. https://doi.org/10.1016/j.cell.2010.04.009
  15. Hanada, T., Noda, N. N., Satomi, Y., Ichimura, Y., Fujioka, Y., Takao, T., Inagaki, F., and Ohsumi, Y. (2007). The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J. Biol. Chem. 282, 37298-37302. https://doi.org/10.1074/jbc.C700195200
  16. Hardwick, K.G., and Pelham, H.R. (1992). SED5 encodes a 39-kD integral membrane protein required for vesicular transport between the ER and the Golgi complex. J. Cell Biol. 119, 513-521. https://doi.org/10.1083/jcb.119.3.513
  17. He, C., and Klionsky, D.J. (2007). Atg9 trafficking in autophagyrelated pathways. Autophagy 3, 271-274. https://doi.org/10.4161/auto.3912
  18. Huang, J., and Klionsky, D.J. (2007). Autophagy and human disease. Cell Cycle 6, 1837-1849. https://doi.org/10.4161/cc.6.15.4511
  19. Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., et al. (2000). A ubiquitin-like system mediates protein lipidation. Nature 408, 488-492. https://doi.org/10.1038/35044114
  20. Kirisako, T., Ichimura, Y., Okada, H., Kabeya, Y., Mizushima, N., Yoshimori, T., Ohsumi, M., Takao, T., Noda, T., and Ohsumi, Y. (2000). The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J. Cell Biol. 151, 263-276. https://doi.org/10.1083/jcb.151.2.263
  21. 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. https://doi.org/10.1083/jcb.119.2.287
  22. Klionsky, D.J., Cuervo, A.M., and Seglen, P.O. (2007). Methods for monitoring autophagy from yeast to human. Autophagy 3, 181-206. https://doi.org/10.4161/auto.3678
  23. Legakis, J.E., Yen, W.L., and Klionsky, D.J. (2007). A cycling protein complex required for selective autophagy. Autophagy 3, 422-432. https://doi.org/10.4161/auto.4129
  24. Lemus, L., and Goder, V. (2016). A SNARE and specific COPII requirements define ER-derived vesicles for the biogenesis of autophagosomes. Autophagy 12, 1049-1050. https://doi.org/10.1080/15548627.2016.1164368
  25. Lemus, L., Ribas, J.L., Sikorska, N., and Goder, V. (2016). An ERlocalized SNARE protein is exported in specific COPII vesicles for autophagosome biogenesis. Cell Rep. 14, 1710-1722. https://doi.org/10.1016/j.celrep.2016.01.047
  26. Li, D., Song, J. Z., Shan, M. H., Li, S. P., Liu, W., Li, H., Zhu, J., Wang, Y., Lin, J., and Xie, Z. (2015). A fluorescent tool set for yeast Atg proteins. Autophagy 11, 954-960. https://doi.org/10.1080/15548627.2015.1040971
  27. Lian, J.P., and Ferro-Novick, S. (1993). Bos1p, an integral membrane protein of the endoplasmic reticulum to Golgi transport vesicles, is required for their fusion competence. Cell 73, 735-745. https://doi.org/10.1016/0092-8674(93)90253-M
  28. Liang, Y., Morozova, N., Tokarev, A.A., Mulholland, J.W., and Segev, N. (2007). The role of Trs65 in the Ypt/Rab guanine nucleotide exchange factor function of the TRAPP II complex. Mol. Biol. Cell 18, 2533-2541. https://doi.org/10.1091/mbc.E07-03-0221
  29. Lynch-Day, M.A., and Klionsky, D.J. (2010). The Cvt pathway as a model for selective autophagy. FEBS Lett. 584, 1359-1366. https://doi.org/10.1016/j.febslet.2010.02.013
  30. 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. USA 107, 7811-7816. https://doi.org/10.1073/pnas.1000063107
  31. Mari, M. and Reggiori, F. (2010). Atg9 reservoirs, a new organelle of the yeast endomembrane system? Autophagy 6, 1221-1223. https://doi.org/10.4161/auto.6.8.13792
  32. 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. J. Cell Biol. 190, 1005-1022. https://doi.org/10.1083/jcb.200912089
  33. Mizushima, N., Levine, B., Cuervo, A.M. and Klionsky, D.J. (2008). Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075. https://doi.org/10.1038/nature06639
  34. Nair, U., Jotwani, A., Geng, J., Gammoh, N., Richerson, D., Yen, W. L., Griffith, J., Nag, S., Wang, K., Moss, T., et al. (2011). SNARE proteins are required for macroautophagy. Cell 146, 290-302. https://doi.org/10.1016/j.cell.2011.06.022
  35. Nakatogawa, H., Ichimura, Y., and Ohsumi, Y. (2007). Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130, 165-178. https://doi.org/10.1016/j.cell.2007.05.021
  36. Nakatogawa, H., Suzuki, K., Kamada, Y., and Ohsumi, Y. (2009). Dynamics and diversity in autophagy mechanisms, lessons from yeast. Nat Rev Mol. Cell Biol. 10, 458-467. https://doi.org/10.1038/nrm2708
  37. Nichols, B. J., and Pelham, H. R. (1998). SNAREs and membrane fusion in the Golgi apparatus. Biochim. Biophys. Acta 1404, 9-31. https://doi.org/10.1016/S0167-4889(98)00044-5
  38. Noda, T., and Klionsky, D.J. (2008). The quantitative Pho8Delta60 assay of nonspecific autophagy. Methods Enzymol. 451, 33-42.
  39. 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. https://doi.org/10.1083/jcb.148.3.465
  40. Obara, K., Sekito, T., and Ohsumi, Y. (2006). Assortment of phosphatidylinositol 3-kinase complexes--Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae. Mol. Biol. Cell 17, 1527-1539. https://doi.org/10.1091/mbc.E05-09-0841
  41. Parlati, F., Varlamov, O., Paz, K., McNew, J.A., Hurtado, D., Sollner, T.H., and Rothman, J.E. (2002). Distinct SNARE complexes mediating membrane fusion in Golgi transport based on combinatorial specificity. Proc. Natl. Acad. Sci. USA 99, 5424-5429. https://doi.org/10.1073/pnas.082100899
  42. Ravikumar, B., Sarkar, S., Davies, J.E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z.W., Jimenez-Sanchez, M., Korolchuk, V.I., Lichtenberg, M., Luo, S., et al. (2010). Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383-1435. https://doi.org/10.1152/physrev.00030.2009
  43. Reggiori, F., and Klionsky, D.J. (2006). Atg9 sorting from mitochondria is impaired in early secretion and VFT-complex mutants in Saccharomyces cerevisiae. J. Cell Sci. 119, 2903-2911. https://doi.org/10.1242/jcs.03047
  44. Reggiori, F., and Klionsky, D. J. (2013). Autophagic processes in yeast, mechanism, machinery and regulation. Genetics 194, 341-361. https://doi.org/10.1534/genetics.112.149013
  45. 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. Dev. Cell 6, 79-90. https://doi.org/10.1016/S1534-5807(03)00402-7
  46. Renna, M., Schaffner, C., Winslow, A.R., Menzies, F.M., Peden, A.A., Floto, R.A., and Rubinsztein, D.C. (2011). Autophagic substrate clearance requires activity of the syntaxin-5 SNARE complex. J. Cell Sci. 124, 469-482. https://doi.org/10.1242/jcs.076489
  47. Sanchez-Wandelmer, J., Ktistakis, N.T., and Reggiori, F. (2015). ERES, sites for autophagosome biogenesis and maturation? J. Cell Sci. 128, 185-192. https://doi.org/10.1242/jcs.158758
  48. Segarra, V.A., Boettner, D.R., and Lemmon, S.K. (2015). Atg27 tyrosine sorting motif is important for its trafficking and Atg9 localization. Traffic 16, 365-378. https://doi.org/10.1111/tra.12253
  49. Segev, N., Mulholland, J., and Botstein, D. (1988). The yeast GTPbinding YPT1 protein and a mammalian counterpart are associated with the secretion machinery. Cell 52, 915-924. https://doi.org/10.1016/0092-8674(88)90433-3
  50. Sogaard, M., Tani, K., Ye, R.R., Geromanos, S., Tempst, P., Kirchhausen, T., Rothman, J.E., and Sollner, T. (1994). A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles. Cell 78, 937-948. https://doi.org/10.1016/0092-8674(94)90270-4
  51. Stanley, R.E., Ragusa, M.J., and Hurley, J.H. (2014). The beginning of the end, how scaffolds nucleate autophagosome biogenesis. Trends. Cell Biol. 24, 73-81. https://doi.org/10.1016/j.tcb.2013.07.008
  52. Suzuki, K., Kubota, Y., Sekito, T., and Ohsumi, Y. (2007). Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12, 209-218. https://doi.org/10.1111/j.1365-2443.2007.01050.x
  53. Tan, D., Cai, Y., Wang, J., Zhang, J., Menon, S., Chou, H.T., Ferro- Novick, S., Reinisch, K.M., and Walz, T. (2013). The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway. Proc. Natl. Acad. Sci. USA 110, 19432-19437. https://doi.org/10.1073/pnas.1316356110
  54. Tanaka, C., Tan, L.J., Mochida, K., Kirisako, H., Koizumi, M., Asai, E., Sakoh-Nakatogawa, M., Ohsumi, Y., and Nakatogawa, H. (2014). Hrr25 triggers selective autophagy-related pathways by phosphorylating receptor proteins. J. Cell Biol. 207, 91-105. https://doi.org/10.1083/jcb.201402128
  55. van der Vaart, A., Griffith, J., and Reggiori, F. (2010). Exit from the Golgi is required for the expansion of the autophagosomal phagophore in yeast Saccharomyces cerevisiae. Mol. Biol. Cell 21, 2270-2284. https://doi.org/10.1091/mbc.E09-04-0345
  56. Wang, J., Menon, S., Yamasaki, A., Chou, H. T., Walz, T., Jiang, Y., and Ferro-Novick, S. (2013). Ypt1 recruits the Atg1 kinase to the preautophagosomal structure. Proc. Natl. Acad. Sci. USA 110, 9800-9805. https://doi.org/10.1073/pnas.1302337110
  57. Wang, J., Tan, D., Cai, Y., Reinisch, K.M., Walz, T., and Ferro-Novick, S. (2014). A requirement for ER-derived COPII vesicles in phagophore initiation. Autophagy 10, 708-709. https://doi.org/10.4161/auto.28103
  58. Wang, J., Davis, S., Menon, S., Zhang, J., Ding, J., Cervantes, S., Miller, E., Jiang, Y., and Ferro-Novick, S. (2015). Ypt1/Rab1 regulates Hrr25/CK1delta kinase activity in ER-Golgi traffic and macroautophagy. J. Cell Biol. 210, 273-285. https://doi.org/10.1083/jcb.201408075
  59. Weinberger, A., Kamena, F., Kama, R., Spang, A., and Gerst, J.E. (2005). Control of Golgi morphology and function by Sed5 t-SNARE phosphorylation. Mol. Biol. Cell 16, 4918-4930. https://doi.org/10.1091/mbc.E05-02-0101
  60. Wooding, S., and Pelham, H.R. (1998). The dynamics of golgi protein traffic visualized in living yeast cells. Mol. Biol. Cell 9, 2667-2680. https://doi.org/10.1091/mbc.9.9.2667
  61. 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. J. Cell Biol. 198, 219-233. https://doi.org/10.1083/jcb.201202061
  62. Yang, Z., and Klionsky, D.J. (2010). Eaten alive, a history of macroautophagy. Nat. Cell Biol. 12, 814-822. https://doi.org/10.1038/ncb0910-814
  63. 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. https://doi.org/10.1091/mbc.e06-07-0612
  64. 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. https://doi.org/10.1083/jcb.200904075
  65. Yla-Anttila, P., Vihinen, H., Jokitalo, E., and Eskelinen, E.L. (2009). 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 5, 1180-1185. https://doi.org/10.4161/auto.5.8.10274
  66. 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. J. Cell Sci. 119, 3888-3900. https://doi.org/10.1242/jcs.03172
  67. Zou, S., Liu, Y., Zhang, C., Yu, S., and Liang, Y. (2015). Bet3 participates in autophagy through GTPase Ypt1 in Saccharomyces cerevisiae. Cell Biol. Int. 39, 466-474. https://doi.org/10.1002/cbin.10416

피인용 문헌

  1. Acetyl-CoA carboxylase 1–dependent lipogenesis promotes autophagy downstream of AMPK vol.294, pp.32, 2017, https://doi.org/10.1074/jbc.ra118.007020
  2. Syntaxin 5 Is Required for the Formation and Clearance of Protein Inclusions during Proteostatic Stress vol.28, pp.8, 2017, https://doi.org/10.1016/j.celrep.2019.07.053
  3. The Golgin Protein RUD3 Regulates Fusarium graminearum Growth and Virulence vol.87, pp.6, 2021, https://doi.org/10.1128/aem.02522-20
  4. Atg9-centered multi-omics integration reveals new autophagy regulators in Saccharomyces cerevisiae vol.17, pp.12, 2021, https://doi.org/10.1080/15548627.2021.1898749