Aggregate clearance of α-synuclein in Saccharomyces cerevisiae depends more on autophagosome and vacuole function than on the proteasome

Journal of Biological Chemistry

Volumn 287, Issue 33, 2012, Pages 27567-27579

  Petroi, Doris ^a,d   Popova, Blagovesta ^a,d   Taheri Talesh, Naimeh ^a,d   Irniger, Stefan ^a,d   Shahpasandzadeh, Hedieh ^a,d   Zweckstetters, Markus ^b,d   Outeiro, Tiago F ^c,d   Braus, Gerhard H ^a,d  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b MAX PLANCK INSTITUTE FOR BIOPHYSICAL CHEMISTRY   (Germany)

^c UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^d Deutsche Forschungsgemeinschaft   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AGGREGATED PROTEIN; AUTOPHAGY; CELLULAR MECHANISMS; DOUBLE MUTANTS; GENETIC VARIANTS; GENOMIC LOCUS; LEWY BODIES; MOLECULAR MECHANISM; NOVEL STRATEGIES; OVER-EXPRESSION; PARKINSON DISEASE; PHENYLMETHYLSULFONYL FLUORIDE; PROTEASOMES; REGULATORY SUBUNITS; SYNUCLEIN; THERAPEUTIC INTERVENTION; VACUOLAR PROTEINS; VACUOLE FUNCTION; WILD TYPES; YEAST CELL; YEAST GROWTH; YEAST SACCHAROMYCES CEREVISIAE;

GENES; YEAST;

AGGREGATES;

ALPHA SYNUCLEIN; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BENZYLSULFONYL FLUORIDE; PROTEASOME;

ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL VACUOLE; CONTROLLED STUDY; FLUORESCENCE MICROSCOPY; FUNGAL STRAIN; FUNGUS GROWTH; FUNGUS MUTANT; GENE DOSAGE; GENE LOCUS; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; NONHUMAN; PLASMID; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN METABOLISM; SACCHAROMYCES CEREVISIAE; SOUTHERN BLOTTING; WILD TYPE;

ALPHA-SYNUCLEIN; AMINO ACID SUBSTITUTION; AUTOPHAGY; HUMANS; LEWY BODIES; MUTATION, MISSENSE; PARKINSON DISEASE; PHAGOSOMES; PROTEASOME ENDOPEPTIDASE COMPLEX; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS; VACUOLES;

EID: 84864979359     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.361865     Document Type: Article

References (75)

1. Galvin, J. E., Lee, V. M., and Trojanowski, J. Q. (2001) Synucleinopathies. clinical and pathological implications. Arch. Neurol. 58, 186-190
2. Forno, L. S., DeLanney, L. E., Irwin, I., and Langston, J. W. (1996) Electron microscopy of Lewy bodies in the amygdala-parahippocampal region. Comparison with inclusion bodies in the MPTP-treated squirrel monkey. Adv. Neurol. 69, 217-228
3. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., and Goedert, M. (1997) α-Synuclein in Lewy bodies. Nature 388, 839-840
4. Maroteaux, L., Campanelli, J. T., and Scheller, R. H. (1988) Synuclein. A neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8, 2804-2815
5. Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, C., Cookson, M. R., Muenter, M., Baptista, M., Miller D., Blancato, J., Hardy J., and Gwinn-Hardy K. (2003) α-Synuclein locus triplication causes Parkinson disease. Science 302, 841
6. Hardy, J., Cai, H., Cookson, M. R., Gwinn-Hardy, K., and Singleton, A. (2006) Genetics of Parkinson disease and parkinsonism. Ann. Neurol. 60, 389-398
7. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G., Lazzarini, A. M., Duvoisin, R. C., Di Iorio, G., Golbe, L. I., and Nussbaum, R. L. (1997) Mutation in the α-synuclein gene identified in families with Parkinson disease. Science 276, 2045-2047
8. Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schöls, L., and Riess, O. (1998) A30P mutation in the gene encoding α-synuclein in Parkinson disease. Nat. Genet. 18, 106-108
9. Giasson, B. I., Uryu, K., Trojanowski, J. Q., and Lee, V. M. (1999) Mutant and wild type human α-synucleins assemble into elongated filaments with distinct morphologies in vitro. J. Biol. Chem. 274, 7619-7622
10. Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., and Lansbury, P. T., Jr. (2002) α-Synuclein, especially the Parkinson disease-associated mutants, forms pore-like annular and tubular protofibrils. J. Mol. Biol. 322, 1089-1102
11. Conway, K. A., Rochet, J. C., Bieganski, R. M., and Lansbury, P. T., Jr. (2001) Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct. Science 294, 1346-1349
12. Volles, M. J., and Lansbury, P. T., Jr. (2002) Vesicle permeabilization by protofibrillar α-synuclein is sensitive to Parkinson disease-linked mutations and occurs by a pore-like mechanism. Biochemistry 41, 4595-4602
13. Karpinar, D. P., Balija, M. B., Kügler, S., Opazo, F., Rezaei-Ghaleh, N., Wender, N., Kim, H. Y., Taschenberger, G., Falkenburger, B. H., Heise, H., Kumar, A., Riedel, D., Fichtner, L., Voigt, A., Braus, G. H., Giller, K., Becker, S., Herzig, A., Baldus, M., Jäckle, H., Eimer, S., Schulz, J. B., Griesinger, C., and Zweckstetter, M. (2009) Pre-fibrillar α-synuclein variants with impaired β-structure increase neurotoxicity in Parkinson disease models. EMBO J. 28, 3256-3268
14. Taschenberger, G., Garrido, M., Tereshchenko, Y., Bähr, M., Zweckstetter, M., and Kügler, S. (2012) Aggregation of α-synuclein promotes progressive in vivo neurotoxicity in adult rat dopaminergic neurons. Acta Neuropathol. 123, 671-683
15. Gajula Balija, M. B., Griesinger, C., Herzig, A., Zweckstetter, M., and Jäckle, H. (2011) Pre-fibrillar α-synuclein mutants cause Parkinson disease-like non-motor symptoms in Drosophila. PLoS One 6, e24701
16. Winner, B., Jappelli, R., Maji, S. K., Desplats, P. A., Boyer, L., Aigner, S., Hetzer, C., Loher, T., Vilar, M., Campioni, S., Tzitzilonis, C., Soragni, A., Jessberger, S., Mira, H., Consiglio, A., Pham, E., Masliah, E., Gage, F. H., and Riek, R. (2011) In vivo demonstration that α-synuclein oligomers are toxic. Proc. Natl. Acad. Sci. U.S.A. 108, 4194-4199
17. Kahle, P. J., Neumann, M., Ozmen, L., and Haass, C. (2000) Physiology and pathophysiology of α-synuclein. Cell culture and transgenic animal models based on a Parkinson disease-associated protein. Ann. N.Y. Acad. Sci. 920, 33-41
18. Matsuoka, Y., Vila, M., Lincoln, S., McCormack, A., Picciano, M., LaFrancois, J., Yu, X., Dickson, D., Langston, W. J., McGowan, E., Farrer, M., Hardy, J., Duff, K., Przedborski, S., and Di Monte, D. A. (2001) Lack of nigral pathology in transgenic mice expressing human α-synuclein driven by the tyrosine hydroxylase promoter. Neurobiol. Dis. 8, 535-539
19. Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., and Lee, V. M. (2002) Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein. Neuron 34, 521-533
20. Outeiro, T. F., and Lindquist, S. (2003) Yeast cells provide insight into α-synuclein biology and pathobiology. Science 302, 1772-1775
21. Lakso, M., Vartiainen, S., Moilanen, A. M., Sirviö, J., Thomas, J. H., Nass, R., Blakely, R. D., and Wong, G. (2003) Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. J. Neurochem. 86, 165-172
22. Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F., Cao, S., Caldwell, K. A., Caldwell, G. A., Marsischky, G., Kolodner, R. D., Labaer, J., Rochet, J. C., Bonini, N. M., and Lindquist, S. (2006) α-Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson models. Science 313, 324-328
23. Bennett, M. C., Bishop, J. F., Leng, Y., Chock, P. B., Chase, T. N., and Mouradian, M. M. (1999) Degradation of α-synuclein by proteasome. J. Biol. Chem. 274, 33855-33858
24. Tofaris, G. K., Layfield, R., and Spillantini, M. G. (2001) α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett. 509, 22-26
25. Ancolio, K., Alves da Costa, C., Uéda, K., and Checler, F. (2000) α-Synuclein and the Parkinson disease-related mutant A53T-α- synuclein do not undergo proteasomal degradation in HEK293 and neuronal cells. Neurosci. Lett. 285, 79-82
26. Lindersson, E., Beedholm, R., Højrup, P., Moos, T., Gai, W., Hendil, K. B., and Jensen, P. H. (2004) Proteasomal inhibition by α-synuclein filaments and oligomers. J. Biol. Chem. 279, 12924-12934
27. Vogiatzi, T., Xilouri, M., Vekrellis, K., and Stefanis, L. (2008) Wild type α-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J. Biol. Chem. 283, 23542-23556
28. Webb, J. L., Ravikumar, B., Atkins, J., Skepper, J. N., and Rubinsztein, D. C. (2003) α-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 278, 25009-25013
29. Winslow, A. R., Chen, C. W., Corrochano, S., Acevedo-Arozena, A., Gordon, D. E., Peden, A. A., Lichtenberg, M., Menzies, F. M., Ravikumar, B., Imarisio, S., Brown, S., O'Kane, C. J., and Rubinsztein, D. C. (2010) α-Synuclein impairs macroautophagy. Implications for Parkinson disease. J. Cell Biol. 190, 1023-1037
30. Anglade, P., Vyas, S., Hirsch, E. C., and Agid, Y. (1997) Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging. Histol. Histopathol. 12, 603-610
31. Sikorski, R. S., and Hieter, P. (1989) A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122, 19-27
32. 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
33. 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
34. Sherman, F. (1991) Getting started with yeast. Methods Enzymol. 194, 3-21
35. Southern, E. M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98, 503-517
36. Hoffman, C. S., and Winston, F. (1987) A 10-min DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene 57, 267-272
37. Abramoff, M., Magelhaes, P., and Ram, S. (2004) Image processing with Image J. Biophotonics Int. 11, 36-42
38. Vida, T. A., and Emr, S. D. (1995) A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. J. Cell Biol. 128, 779-792
39. Lee, D. H., and Goldberg, A. L. (1996) Selective inhibitors of the proteasome-dependent and vacuolar pathways of protein degradation in Saccharomyces cerevisiae. J. Biol. Chem. 271, 27280-27284
40. 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
41. Dixon, C., Mathias, N., Zweig, R. M., Davis, D. A., and Gross, D. S. (2005) α-Synuclein targets the plasma membrane via the secretory pathway and induces toxicity in yeast. Genetics 170, 47-59
42. Lamphier, M. S., and Ptashne, M. (1992) Multiple mechanisms mediate glucose repression of the yeast GAL1 gene. Proc. Natl. Acad. Sci. U.S.A. 89, 5922-5926
43. Lee, D. H., and Goldberg, A. L. (1998) Proteasome inhibitors. Valuable new tools for cell biologists. Trends Cell Biol. 8, 397-403
44. Ghislain, M., Udvardy, A., and Mann, C. (1993) S. cerevisiae 26 S protease mutants arrest cell division in G2/metaphase. Nature 366, 358-362
45. Jones, E. W. (2002) Vacuolar proteases and proteolytic artifacts in Saccharomyces cerevisiae. Methods Enzymol. 351, 127-150
46. Dubiel, W., Ferrell, K., Pratt, G., and Rechsteiner, M. (1992) Subunit 4 of the 26 S protease is a member of a novel eukaryotic ATPase family. J. Biol. Chem. 267, 22699-22702
47. Matsuura, A., Tsukada, M., Wada, Y., and Ohsumi, Y. (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192, 245-250
48. Parr, C. L., Keates, R. A., Bryksa, B. C., Ogawa, M., and Yada, R. Y. (2007) The structure and function of Saccharomyces cerevisiae proteinase A. Yeast 24, 467-480
49. Woolford, C. A., Daniels, L. B., Park, F. J., Jones, E. W., Van Arsdell, J. N., and Innis, M. A. (1986) The PEP4 gene encodes an aspartyl protease implicated in the posttranslational regulation of Saccharomyces cerevisiae vacuolar hydrolases. Mol. Cell. Biol. 6, 2500-2510
50. Kamada, Y., Sekito, T., and Ohsumi, Y. (2004) Autophagy in yeast. A TOR-mediated response to nutrient starvation. Curr. Top Microbiol. Immunol. 279, 73-84
51. Wong, G. K., Griffith, S., Kojima, I., and Demain, A. L. (1998) Antifungal activities of rapamycin and its derivatives, prolylrapamycin, 32-desmethylrapamycin, and 32-desmethoxyrapamycin. J. Antibiot. 51, 487-491
52. Karube, H., Sakamoto, M., Arawaka, S., Hara, S., Sato, H., Ren, C. H., Goto, S., Koyama, S., Wada, M., Kawanami, T., Kurita, K., and Kato, T. (2008) N-terminal region of α-synuclein is essential for the fatty acid-induced oligomerization of the molecules. FEBS Lett. 582, 3693-3700
53. Cookson, M. R. (2005) The biochemistry of Parkinson disease. Annu. Rev. Biochem. 74, 29-52
54. Murray, I. V., Giasson, B. I., Quinn, S. M., Koppaka, V., Axelsen, P. H., Ischiropoulos, H., Trojanowski, J. Q., and Lee, V. M. (2003) Role of α-synuclein carboxyl terminus on fibril formation in vitro. Biochemistry 42, 8530-8540
55. Tsigelny, I. F., Bar-On, P., Sharikov, Y., Crews, L., Hashimoto, M., Miller, M. A., Keller, S. H., Platoshyn, O., Yuan, J. X., and Masliah, E. (2007) Dynamics of α-synuclein aggregation and inhibition of pore-like oligomer development by β-synuclein. FEBS J. 274, 1862-1877
56. Müller, O., Sattler, T., Flötenmeyer, M., Schwarz, H., Plattner, H., and Mayer, A. (2000) Autophagic tubes. Vacuolar invaginations involved in lateral membrane sorting and inverse vesicle budding. J. Cell Biol. 151, 519-528
57. Outeiro, T. F., Putcha, P., Tetzlaff, J. E., Spoelgen, R., Koker, M., Carvalho, F., Hyman, B. T., and McLean, P. J. (2008) Formation of toxic oligomeric α-synuclein species in living cells. PLoS One 3, e1867
58. Chen, L., and Feany, M. B. (2005) α-Synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat. Neurosci. 8, 657-663
59. Volles, M. J., and Lansbury, P. T., Jr. (2007) Relationships between the sequence of α-synuclein and its membrane affinity, fibrillization propensity, and yeast toxicity. J. Mol. Biol. 366, 1510-1522
60. Kim, Y. S., Laurine, E., Woods, W., and Lee, S. J. (2006) A novel mechanism of interaction between α-synuclein and biological membranes. J. Mol. Biol. 360, 386-397
61. Opazo, F., Krenz, A., Heermann, S., Schulz, J. B., and Falkenburger, B. H. (2008) Accumulation and clearance of α-synuclein aggregates demonstrated by time-lapse imaging. J. Neurochem. 106, 529-540
62. Riedel, M., Goldbaum, O., Schwarz, L., Schmitt, S., and Richter-Landsberg, C. (2010) 17-AAG induces cytoplasmic α-synuclein aggregate clearance by induction of autophagy. PLoS One 5, e8753
63. Fortun, J., Dunn, W. A., Jr., Joy, S., Li, J., and Notterpek, L. (2003) Emerging role for autophagy in the removal of aggresomes in Schwann cells. J. Neurosci. 23, 10672-10680
64. Dyllick-Brenzinger, M., D'Souza, C. A., Dahlmann, B., Kloetzel, P. M., and Tandon, A. (2010) Reciprocal effects of α-synuclein overexpression and proteasome inhibition in neuronal cells and tissue. Neurotox Res. 17, 215-227
65. Flower, T. R., Clark-Dixon, C., Metoyer, C., Yang, H., Shi, R., Zhang, Z., and Witt, S. N. (2007) YGR198w (YPP1) targets A30P α-synuclein to the vacuole for degradation. J. Cell Biol. 177, 1091-1104
66. Paxinou, E., Chen, Q., Weisse, M., Giasson, B. I., Norris, E. H., Rueter, S. M., Trojanowski, J. Q., Lee, V. M., and Ischiropoulos, H. (2001) Induction of α-synuclein aggregation by intracellular nitrative insult. J. Neurosci. 21, 8053-8061
67. Chen, Q., Thorpe, J., and Keller, J. N. (2005) α-synuclein alters proteasome function, protein synthesis, and stationary phase viability. J. Biol. Chem. 280, 30009-30017
68. Bedford, L., Hay, D., Devoy, A., Paine, S., Powe, D. G., Seth, R., Gray, T., Topham, I., Fone, K., Rezvani, N., Mee, M., Soane, T., Layfield, R., Sheppard, P. W., Ebendal, T., Usoskin, D., Lowe, J., and Mayer, R. J. (2008) Depletion of 26 S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies. J. Neurosci. 28, 8189-8198
69. McNaught, K. S., and Jenner, P. (2001) Proteasomal function is impaired in substantia nigra in Parkinson disease. Neurosci. Lett. 297, 191-194
70. Rideout, H. J., Lang-Rollin, I., and Stefanis, L. (2004) Involvement of macroautophagy in the dissolution of neuronal inclusions. Int. J. Biochem. Cell Biol. 36, 2551-2562
71. Olanow, C. W., and McNaught, K. S. (2006) Ubiquitin-proteasome system and Parkinson disease. Mov. Disord. 21, 1806-1823
72. Tofaris, G. K., Kim, H. T., Hourez, R., Jung, J. W., Kim, K. P., and Goldberg, A. L. (2011) Ubiquitin ligase Nedd4 promotes α-synuclein degradation by the endosomal-lysosomal pathway. Proc. Natl. Acad. Sci. U.S.A. 108, 17004-17009
73. Soper, J. H., Kehm, V., Burd, C. G., Bankaitis, V. A., and Lee, V. M. (2011) Aggregation of α-synuclein in S. cerevisiae is associated with defects in endosomal trafficking and phospholipid biosynthesis. J. Mol. Neurosci. 43, 391-405
74. Gitler, A. D., Bevis, B. J., Shorter, J., Strathearn, K. E., Hamamichi, S., Su, L. J., Caldwell, K. A., Caldwell, G. A., Rochet, J. C., McCaffery, J. M., Barlowe, C., and Lindquist, S. (2008) The Parkinson disease protein α-synuclein disrupts cellular Rab homeostasis. Proc. Natl. Acad. Sci. U.S.A. 105, 145-150
75. Xilouri, M., Vogiatzi, T., Vekrellis, K., Park, D., and Stefanis, L. (2009) Abberant α-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy. PLoS One 4, e5515