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The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Dynein mutations impair autophagic clearance of aggregate-prone proteins

Ravikumar, Brinda, Acevedo-Arozena, Abraham, Imarisio, Sara, Berger, Zdenek, Vacher, Coralie, O'Kane, Cahir J, Brown, Steve D M, Rubinsztein, David C·2005·Nature Genetics
DOI 10.1038/ng1591
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Abstract

Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease. Here we identify a new mechanism of inclusion formation by showing that decreased dynein function impairs autophagic clearance of aggregate-prone proteins. We show that mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models. Furthermore, loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II in both cell culture and mouse models, compatible with impaired autophagosome-lysosome fusion.

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Crossref · 10.1038/ng1591

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4 of 4 references verified0 citation errors · 0 not checkable

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  • Defects in induction, maturation, or lysosomal clearance impair protein degradation.

    “Defects in induction, maturation, or lysosomal clearance impair protein degradation (Zhong et al. 2009), (Pickford et al. 2008), (Ravikumar et al. 2005), (Webb et al. 2004), (Iwata et al. 2005), (Kimura et al. 2008), (Wong and Cuervo 2010), (Lee et al. 2010), and is assessable via LC3-II turnover or p62 degradation (Mizushima et al. 2010), (Ju et al. 2010), (Klionsky et al. 2008b), (Tanida et al.”

    From TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models (2026) · cites this paper as Ravikumar et al. 2005

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Research works printed but not linked: 26

  1. Hafezparast, M. et al. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300, 808–812 (2003). · DOI
  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). · DOI
  3. Puls, I. et al. Mutant dynactin in motor neuron disease. Nat. Genet. 33, 455–456 (2003). · DOI
  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). · DOI
  5. Cleveland, D.W. From Charcot to SOD1: mechanisms of selective motor neuron death in ALS. Neuron 24, 515–520 (1999). · DOI
  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). · DOI
  7. Szebenyi, G. et al. Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 40, 41–52 (2003). · DOI
  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). · DOI · Paper page
  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). · DOI · Paper page
  10. Leigh, P.N. et al. Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 114, 775–788 (1991). · DOI
  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). · DOI
  12. Mizushima, N., Ohsumi, Y. & Yoshimori, T. Autophagosome formation in mammalian cells. Cell Struct. Funct. 27, 421–429 (2002). · DOI
  13. 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). · DOI
  14. 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). · DOI
  15. Ekstrom, P. & Kanje, M. Inhibition of fast axonal transport by erythro-9-[3-(2-hydroxynonyl)]adenine. J. Neurochem. 43, 1342–1345 (1984). · DOI
  16. 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). · DOI
  17. 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). · DOI · Paper page
  18. Quintyne, N.J. et al. Dynactin is required for microtubule anchoring at centrosomes. J. Cell Biol. 147, 321–334 (1999). · DOI
  19. 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). · DOI
  20. 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). · DOI
  21. 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). · DOI · Paper page
  22. Jackson, G.R. et al. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 21, 633–642 (1998). · DOI
  23. 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). · DOI
  24. 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). · DOI · Paper page
  25. Taylor, J.P. et al. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum. Mol. Genet. 12, 749–757 (2003). · DOI
  26. 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). · DOI

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Metadata

Authors
Ravikumar, B., Acevedo-Arozena, A., Imarisio, S., Berger, Z., Vacher, C., O'Kane, C. J., Brown, S. D. M., & Rubinsztein, D. C.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2005-06-26
Volume
37
Issue
7
Pages
771-776
ISSN
  • 1061-4036
  • 1546-1718
DOI
10.1038/ng1591
Cited by
416
References
4
Language
en
Licence
www.springer.com/tdm (tdm)

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