α-Synuclein impairs macroautophagy: implications for Parkinson's disease. (original) (raw)
Winslow, A.R., Chen, C.W., Corrochano, S. et al. (10 more authors) (2010)α-Synuclein impairs macroautophagy: implications for Parkinson's disease. Journal of Cell Biology, 190 (6). pp. 1023-1037. ISSN 0021-9525
Abstract
Parkinson's disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplication of the α-synuclein gene locus increases α-synuclein expression and causes PD. Thus, overexpression of wild-type α-synuclein is toxic. In this study, we demonstrate that α-synuclein overexpression impairs macroautophagy in mammalian cells and in transgenic mice. Our data show that α-synuclein compromises autophagy via Rab1a inhibition and Rab1a overexpression rescues the autophagy defect caused by α-synuclein. Inhibition of autophagy by α-synuclein overexpression or Rab1a knockdown causes mislocalization of the autophagy protein, Atg9, and decreases omegasome formation. Rab1a, α-synuclein, and Atg9 all regulate formation of the omegasome, which marks autophagosome precursors.
Metadata
| Authors/Creators: | Winslow, A.R.Chen, C.W.Corrochano, S.Acevedo-Arozena, A.Gordon, D.E.Peden, A.A.  https://orcid.org/0000-0003-0144-7712Lichtenberg, M.Menzies, F.M.Ravikumar, B.Imarisio, S.Brown, S.O'Kane, C.J.Rubinsztein, D.C. |
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| Copyright, Publisher and Additional Information: | © 2010 Winslow et al. Reproduced in accordance with the publisher's self-archiving policy. |
| Keywords: | Animals; Autophagy; Cell Line, Tumor; Drosophila melanogaster; Gene Knockdown Techniques; Golgi Apparatus; Humans; Membrane Proteins; Mice; Microtubule-Associated Proteins; Models, Biological; Parkinson Disease; Phagosomes; Protein Transport; Secretory Vesicles; alpha-Synuclein; rab1 GTP-Binding Proteins |
| Dates: | Published: 20 September 2010 |
| Institution: | The University of Sheffield |
| Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
| Depositing User: | Symplectic Sheffield |
| Date Deposited: | 22 Feb 2017 11:43 |
| Last Modified: | 22 Feb 2017 11:43 |
| Published Version: | https://doi.org/10.1083/jcb.201003122 |
| Status: | Published |
| Publisher: | Rockefeller University Press |
| Refereed: | Yes |
| Identification Number: | https://doi.org/10.1083/jcb.201003122 |
| Related URLs: | Author |