Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast
The budding yeast Saccharomyces cerevisiae represents an established model system to study the molecular mechanisms associated to neurodegenerative disorders. A key-feature of Parkinson’s disease is the formation of Lewy bodies, which are cytoplasmic protein inclusions. Misfolded α-synuclein is one...
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| Format: | Online |
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MDPI
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496687/ |
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pubmed-4496687 |
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pubmed-44966872015-07-10 Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast Popova, Blagovesta Kleinknecht, Alexandra Braus, Gerhard H. Review The budding yeast Saccharomyces cerevisiae represents an established model system to study the molecular mechanisms associated to neurodegenerative disorders. A key-feature of Parkinson’s disease is the formation of Lewy bodies, which are cytoplasmic protein inclusions. Misfolded α-synuclein is one of their main constituents. Expression of α-synuclein protein in yeast leads to protein aggregation and cellular toxicity, which is reminiscent to Lewy body containing human cells. The molecular mechanism involved in clearance of α-synuclein aggregates is a central question for elucidating the α-synuclein-related toxicity. Cellular clearance mechanisms include ubiquitin mediated 26S proteasome function as well as lysosome/vacuole associated degradative pathways as autophagy. Various modifications change α-synuclein posttranslationally and alter its inclusion formation, cytotoxicity and the distribution to different clearance pathways. Several of these modification sites are conserved from yeast to human. In this review, we summarize recent findings on the effect of phosphorylation and sumoylation of α-synuclein to the enhanced channeling to either the autophagy or the proteasome degradation pathway in yeast model of Parkinson’s disease. MDPI 2015-04-23 /pmc/articles/PMC4496687/ /pubmed/25915624 http://dx.doi.org/10.3390/biom5020617 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Popova, Blagovesta Kleinknecht, Alexandra Braus, Gerhard H. |
| spellingShingle |
Popova, Blagovesta Kleinknecht, Alexandra Braus, Gerhard H. Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast |
| author_facet |
Popova, Blagovesta Kleinknecht, Alexandra Braus, Gerhard H. |
| author_sort |
Popova, Blagovesta |
| title |
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast |
| title_short |
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast |
| title_full |
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast |
| title_fullStr |
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast |
| title_full_unstemmed |
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast |
| title_sort |
posttranslational modifications and clearing of α-synuclein aggregates in yeast |
| description |
The budding yeast Saccharomyces cerevisiae represents an established model system to study the molecular mechanisms associated to neurodegenerative disorders. A key-feature of Parkinson’s disease is the formation of Lewy bodies, which are cytoplasmic protein inclusions. Misfolded α-synuclein is one of their main constituents. Expression of α-synuclein protein in yeast leads to protein aggregation and cellular toxicity, which is reminiscent to Lewy body containing human cells. The molecular mechanism involved in clearance of α-synuclein aggregates is a central question for elucidating the α-synuclein-related toxicity. Cellular clearance mechanisms include ubiquitin mediated 26S proteasome function as well as lysosome/vacuole associated degradative pathways as autophagy. Various modifications change α-synuclein posttranslationally and alter its inclusion formation, cytotoxicity and the distribution to different clearance pathways. Several of these modification sites are conserved from yeast to human. In this review, we summarize recent findings on the effect of phosphorylation and sumoylation of α-synuclein to the enhanced channeling to either the autophagy or the proteasome degradation pathway in yeast model of Parkinson’s disease. |
| publisher |
MDPI |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496687/ |
| _version_ |
1613245994528407552 |