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 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.
Department of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, Germany. bpopova@gwdg.de.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), D-37077 Göttingen, Germany. bpopova@gwdg.de.
Blagovesta
B
Popova
Department of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, Germany. ajucker@gwdg.de.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), D-37077 Göttingen, Germany. ajucker@gwdg.de.
Alexandra
A
Kleinknecht
Department of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, Germany. gbraus@gwdg.de.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), D-37077 Göttingen, Germany. gbraus@gwdg.de.
Gerhard H
GH
Braus
D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism*; D066329:Protein Aggregates; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D066329:Protein Aggregates; D051844:alpha-Synuclein