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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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Detalles Bibliográficos
Autores principales: Popova, Blagovesta, Kleinknecht, Alexandra, Braus, Gerhard H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496687/
https://www.ncbi.nlm.nih.gov/pubmed/25915624
http://dx.doi.org/10.3390/biom5020617
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author Popova, Blagovesta
Kleinknecht, Alexandra
Braus, Gerhard H.
author_facet Popova, Blagovesta
Kleinknecht, Alexandra
Braus, Gerhard H.
author_sort Popova, Blagovesta
collection PubMed
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.
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spelling pubmed-44966872015-07-10 Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast Popova, Blagovesta Kleinknecht, Alexandra Braus, Gerhard H. Biomolecules 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/).
spellingShingle Review
Popova, Blagovesta
Kleinknecht, Alexandra
Braus, Gerhard H.
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast
title 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_short Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast
title_sort posttranslational modifications and clearing of α-synuclein aggregates in yeast
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496687/
https://www.ncbi.nlm.nih.gov/pubmed/25915624
http://dx.doi.org/10.3390/biom5020617
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