α-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models

Science

Volumn 313, Issue 5785, 2006, Pages 324-328

  Cooper, Antony A ^a,j   Gitler, Aaron D ^b   Cashikar, Anil ^b,k   Haynes, Cole M ^a,l   Hill, Kathryn J ^a,j   Bhullar, Bhupinder ^b,c   Liu, Kangning ^d,e   Xu, Kexiang ^d   Strathearn, Katharine E ^f   Liu, Fang ^f   Cao, Songsong ^g   Caldwell, Kim A ^g   Caldwell, Guy A ^g   Marsischky, Gerald ^c   Kolodner, Richard D ^h   LaBaer, Joshua ^c   Rochet, Jean Christophe ^f   Bonini, Nancy M ^d,e   Lindquist, Susan ^b,i  

^a UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

^b WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

^c Department of Biological Chemistry and Molecular Pharmacology   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^f PURDUE UNIVERSITY   (United States)

^g UNIVERSITY OF ALABAMA   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^j GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^k MEDICAL COLLEGE OF GEORGIA   (United States)

^l NEW YORK UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; DISEASES; GENES; PROTEINS; YEAST;

GOLGI VESICULAR TRAFFICKING; NEURON LOSS; PARKINSON'S DISEASE (PD); PATHOBIOLOGY;

NEUROLOGY;

ALPHA SYNUCLEIN; GUANOSINE TRIPHOSPHATASE; PROTEIN RAB1; PROTEIN YPT1P; RAB PROTEIN; UNCLASSIFIED DRUG; DOPAMINE; HYBRID PROTEIN; PROTEASOME; PROTEIN; SACCHAROMYCES CEREVISIAE PROTEIN; YPT1 PROTEIN, S CEREVISIAE;

ACCUMULATION RATE; CELL ORGANELLE; DISEASE INCIDENCE; TOXIC SUBSTANCE; TOXICITY; YEAST;

ARTICLE; CELL FUNCTION; DEGENERATIVE DISEASE; DRUG CYTOTOXICITY; ENDOPLASMIC RETICULUM; GENE; GOLGI COMPLEX; HUMAN; MEMBRANE TRANSPORT; NERVE CELL NECROSIS; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN FUNCTION; YEAST CELL; YPT1 GENE; ANIMAL; CAENORHABDITIS ELEGANS; CELL CULTURE; CELL SURVIVAL; CHEMISTRY; CYTOLOGY; DISEASE MODEL; DROSOPHILA; GENE EXPRESSION; GENE LIBRARY; GENETICS; METABOLISM; MOUSE; NERVE CELL; NERVE DEGENERATION; PARKINSONISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PROTEIN TRANSPORT; RAT; SACCHAROMYCES CEREVISIAE; TRANSGENIC ANIMAL;

ANIMALIA; MAMMALIA;

ALPHA-SYNUCLEIN; ANIMALS; ANIMALS, GENETICALLY MODIFIED; CAENORHABDITIS ELEGANS; CELL SURVIVAL; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DOPAMINE; DROSOPHILA; ENDOPLASMIC RETICULUM; GENE EXPRESSION; GENE LIBRARY; GOLGI APPARATUS; HUMANS; MICE; NERVE DEGENERATION; NEURONS; PARKINSONIAN DISORDERS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN FOLDING; PROTEIN TRANSPORT; PROTEINS; RAB GTP-BINDING PROTEINS; RAB1 GTP-BINDING PROTEINS; RATS; RECOMBINANT FUSION PROTEINS; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 33746533924     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1129462     Document Type: Article

References (34)

1. M. Vila, S. Przedborski, Nat. Med. 10 (Suppl.), 558 (2004).
2. M. S. Forman, J. Q. Trojanowski, V. M. Lee, Nat. Med. 10, 1055 (2004).
3. M. G. Spillantini, R. A. Crowther, R. Jakes, M. Hasegawa, M. Goedert, Proc. Natl. Acad. Sci U.S.A 95, 6469 (1998).
4. M. H. Polymeropoulos et al., Science 276, 2045 (1997).
5. R. Kruger et al., Nat. Genet. 18, 106 (1998).
6. J. J. Zarranz et al., Ann. Neurol. 55, 164 (2004).
7. A. B. Singleton et al., Science 302, 841 (2003).
8. M. C. Chartier-Harlin et al., Lancet 364, 1167 (2004).
9. P. Ibanez et al., Lancet 364, 1169 (2004).
10. P. K. Auluck, H. Y. Chan, J. Q. Trojanowski, V. M. Lee, N. M. Bonini, Science 295, 865 (2002).
11. C. Lo Bianco, J. L. Ridet, B. L. Schneider, N. Deglon, P. Aebischer, Proc. Natl. Acad. Sci. U.S.A. 99, 10813 (2002).
12. E. Masliah et al., Science 287, 1265 (2000).
13. S. Cao, C. C. Gelwix, K. A. Caldwell, G. A. Caldwell, J. Neurosci. 25, 3801 (2005).
14. W. Dauer, S. Przedborski, Neuron 39, 889 (2003).
15. T. F. Outeiro, S. Lindquist, Science 302, 1772 (2003).
16. A. A. McCracken, J. L. Brodsky, Bioessays 25, 868 (2003).
17. M. Hochstrasser, A. Varshavsky, Cell 61, 697 (1990).
18. M. Knop, N. Hauser, D. H. Wolf, Yeast 12, 1229 (1996).
19. T. Biederer, C. Volkwein, T. Sommer, EMBO J. 15, 2069 (1996).
20. S. R. Caldwell, K. J. Hill, A. A. Cooper, J. Biol. Chem. 276, 23296 (2001).
21. E. D. Spear, D. T. Ng, Mol. Biol. Cell 14, 2756 (2003).
22. D. J. Klionsky, S. D. Emr, EMBO J. 8, 2241 (1989).
23. T. Stevens, B. Esmon, R. Schekman, Cell 30, 439 (1982).
24. Materials and methods are available as supporting material on Science Online.
25. R. Ossig, C. Dascher, H. H. Trepte, H. D. Schmitt, D. Gallwitz, Mol. Cell. Biol. 11, 2980 (1991).
26. D. L. Fortin et al., J. Neurosci. 24, 6715 (2004).
27. J. C. Rochet et al., J. Mol. Neurosci. 23, 23 (2004).
28. B. S. Wilson et al., J. Cell Biol. 125, 557 (1994).
29. N. Gosavi, H. J. Lee, J. S. Lee, S. Patel, S. J. Lee, J. Biol. Chem. 277, 48984 (2002).
30. E. J. Ryu et al., J. Neurosci. 22, 10690 (2002).
31. M. Cohen, F. Stutz, N. Belgareh, R. Haguenauer-Tsapis, C. Dargemont, Nat. Cell Biol. 5, 661 (2003).
32. S. Chandra, G. Gallardo, R. Fernandez-Chacon, O. M. Schluter, T. C. Sudhof, Cell 123, 383 (2005).
33. J. Lotharius et al., J. Biol. Chem. 277, 38884 (2002).
34. We thank D. Eide, M. Hochstrasser, J. Warner, and R. Collins for plasmids. We are grateful to members of the Lindquist lab for helpful suggestions and comments on the manuscript, especially J. Shorter and B. Bevis for advice and encouragement and T. Outeiro for making the screening strain. A.D.G. is a Lilly Fellow of the Life Sciences Research Foundation. The YEASTFlex collection was supported by National Human Genome Research Institute grant R01-HG002923. This work was supported by NIH (A.A.C.; Udall Center, S.L.; J.-C.R.; G.A.C.), Missouri Alzheimer's Grant (A.A.C), National Institute on Aging (N.M.B.), and the McKnight Fund for Neuroscience. (S.L). S.L. and N.M.B. are investigators of the Howard Hughes Medical Institute. S.L. is a founder and former member of the Board of Directors of, and has received consulting fees from, FoldRx Pharmaceuticals, a company that investigates drugs to treat protein-folding diseases. She holds a patent on modulators of α-synuclein toxicity; genes described in the patent are licensed to FoIdRx Pharmaceuticals. She is also a member of the Board of Directors of Johnson & Johnson. A.A.C. and J.-C.R. have received consulting fees from FoldRx Pharmaceuticals, and J.-C R. has received payment from FoldRx for testing drugs in his laboratory.