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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doaj-8665269c3e2e4b9b9dea8f60523743da2020-11-24T20:58:00ZengMDPI AGBiomolecules2218-273X2015-04-015261763410.3390/biom5020617biom5020617Posttranslational Modifications and Clearing of α-Synuclein Aggregates in YeastBlagovesta Popova0Alexandra Kleinknecht1Gerhard H. Braus2Department of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, GermanyDepartment of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, GermanyDepartment of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, GermanyThe 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.http://www.mdpi.com/2218-273X/5/2/617α-synucleinParkinson’s diseaseyeastposttranslational modificationsaggregate clearanceautophagyproteasome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Blagovesta Popova Alexandra Kleinknecht Gerhard H. Braus |
spellingShingle |
Blagovesta Popova Alexandra Kleinknecht Gerhard H. Braus Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast Biomolecules α-synuclein Parkinson’s disease yeast posttranslational modifications aggregate clearance autophagy proteasome |
author_facet |
Blagovesta Popova Alexandra Kleinknecht Gerhard H. Braus |
author_sort |
Blagovesta Popova |
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 |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2015-04-01 |
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. |
topic |
α-synuclein Parkinson’s disease yeast posttranslational modifications aggregate clearance autophagy proteasome |
url |
http://www.mdpi.com/2218-273X/5/2/617 |
work_keys_str_mv |
AT blagovestapopova posttranslationalmodificationsandclearingofasynucleinaggregatesinyeast AT alexandrakleinknecht posttranslationalmodificationsandclearingofasynucleinaggregatesinyeast AT gerhardhbraus posttranslationalmodificationsandclearingofasynucleinaggregatesinyeast |
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1716786765948256256 |