Dynein mutations impair autophagic clearance of aggregate-prone proteins

Nature Genetics

Volumn 37, Issue 7, 2005, Pages 771-776

  Ravikumar, Brinda ^a   Acevedo Arozena, Abraham ^b   Imarisio, Sara ^a,c   Berger, Zdenek ^a,c   Vacher, Coralie ^a   O'Kane, Cahir J ^c   Brown, Steve D M ^b   Rubinsztein, David C ^a  

^a ADDENBROOKE S HOSPITAL   (United Kingdom)

^b MRC MAMMALIAN GENETICS UNIT   (United Kingdom)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DYNEIN ADENOSINE TRIPHOSPHATASE; HUNTINGTIN; 9 (2 HYDROXY 3 NONYL)ADENINE; 9-(2-HYDROXY-3-NONYL)ADENINE; ADENINE; ADENYLYLIMIDODIPHOSPHATE; DRUG DERIVATIVE; HD PROTEIN, HUMAN; HDH PROTEIN, MOUSE; HDH PROTEIN, RAT; NERVE PROTEIN; NUCLEAR PROTEIN; PROTEASOME; SYNUCLEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL CULTURE; CELL STRAIN; CONTROLLED STUDY; HUNTINGTON CHOREA; IMMUNOCYTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; KIDNEY CELL; LYSOSOME; MOTOR NEURON DISEASE; MUTATION; NONHUMAN; PRIORITY JOURNAL; RAT; WESTERN BLOTTING; ANIMAL; ANIMAL BEHAVIOR; AUTOPHAGY; BRAIN; CELL INCLUSION; CELL STRAIN COS1; CERCOPITHECUS; CROSS BREEDING; DRUG ANTAGONISM; FLY; GENETICS; HUMAN; METABOLISM; MOUSE; MOUSE MUTANT; PATHOLOGY;

ANIMALIA;

ADENINE; ADENYLYL IMIDODIPHOSPHATE; ANIMALS; AUTOPHAGY; BEHAVIOR, ANIMAL; BRAIN; CERCOPITHECUS AETHIOPS; COS CELLS; CROSSES, GENETIC; DIPTERA; DYNEIN ATPASE; HUMANS; HUNTINGTON DISEASE; INCLUSION BODIES; MICE; MICE, MUTANT STRAINS; MUTATION; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; PC12 CELLS; PROTEASOME ENDOPEPTIDASE COMPLEX; RATS; SYNUCLEINS;

EID: 22844436451     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng1591     Document Type: Article

References (30)

1. Hafezparast, M. et al. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300, 808-812 (2003).
2. LaMonte, B.H. et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34, 715-727 (2002).
3. Puls, I. et al. Mutant dynactin in motor neuron disease. Nat. Genet. 33, 455-456 (2003).
4. Goldstein, L.S. & Yang, Z. Microtubule-based transport systems in neurons: the roles of kinesins and dyneins. Annu. Rev. Neurosci. 23, 39-71 (2000).
5. Cleveland, D.W. From Charcot to SOD1: mechanisms of selective motor neuron death in ALS. Neuron 24, 515-520 (1999).
6. Gunawardena, S. et al. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 40, 25-40 (2003).
7. Szebenyi, G. et al. Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 40, 41-52 (2003).
8. Trushina, E. et al. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell. Biol. 24, 8195-8209 (2004).
9. Ishihara, T. et al. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24, 751-762 (1999).
10. Leigh, P.N. et al. Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 114, 775-788 (1991).
11. Ravikumar, B., Duden, R. & Rubinsztein, D.C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Genet. 11, 1107-1117 (2002).
12. Webb, J.L., Ravikumar, B., Atkins, J., Skepper, J.N. & Rubinsztein, D.C. Alpha-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 278, 25009-25013 (2003).
13. Cuervo, A.M., Stefanis, L., Fredenburg, R., Lansbury, P.T. & Sulzer, D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305, 1292-1295 (2004).
14. Mizushima, N., Ohsumi, Y, & Yoshimori, T. Autophagosome formation in mammalian cells. Cell Struct. Funct. 27, 421-429 (2002).
15. Webb, J.L., Ravikumar, B. & Rubinsztein, D.C. Microtubule disruption inhibits autophagosome-lysosome fusion: implications for studying the roles of aggresomes in polyglutamine diseases. Int. J. Biochem. Cell Biol. 36, 2541-2550 (2004).
16. Narain, Y., Wyttenbach, A., Rankin, J., Furlong, R.A. & Rubinsztein, D.C. A molecular investigation of true dominance in Huntington's disease. J. Med. Genet. 36, 739-746 (1999).
17. Ekstrom, P. & Kanje, M. Inhibition of fast axonal transport by erythro-9-[3-(2-hydroxynonyl)]adenine. J. Neurochem. 43, 1342-1345 (1984).
18. Bananis, E., Murray, J.W., Stockert, R.J., Satir, P. & Wolkoff, A.W. Microtubule and motor-dependent endocytic vesicle sorting in vitro. J. Cell Biol. 151, 179-186 (2000).
19. Dantuma, N.P., Lindsten, K., Glas, R., Jellne, M. & Masucci, M.G. Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome- dependent proteolysis in living cells. Nat. Biotechnol. 18, 538-543 (2000).
20. Quintyne, N.J. et al. Dynactin is required for microtubule anchoring at centrosomes. J. Cell Biol. 147, 321-334 (1999).
21. Wubbolts, R. et al. Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments. J. Cell Sci. 112, 785-795 (1999).
22. Bannai, H., Inoue, T., Nakayama, T., Hattori, M. & Mikoshiba, K. Kinesin dependent, rapid, bi-directional transport of ER sub-compartment in dendrites of hippocampal neurons. J. Cell Sci. 117, 163-175 (2004).
23. Kabeya, Y. et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19, 5720-5728 (2000).
24. Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T. & Ohsumi, Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101-1111 (2004).
25. Jackson, G.R. et al. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 21, 633-642 (1998).
26. Schilling, G. et al. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 8, 397-407 (1999).
27. Rogers, D.C. et al. SHIRPA, a protocol for behavioral assessment: validation for longitudinal study of neurological dysfunction in mice. Neurosci. Lett. 306, 89-92 (2001).
28. Ravikumar, B. et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36, 585-595 (2004).
29. Taylor, J.P. et al. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum. Mol. Genet. 12, 749-757 (2003).
30. Bauvy, C., Gane, P., Arico, S., Codogno, P. & Ogier-Denis, E. Autophagy delays sulindac sulfide-induced apoptosis in the human intestinal colon cancer cell line HT-29. Exp. Cell Res. 268, 139-149 (2001).