Journal article
Contribution of Alanine-76 and Serine Phosphorylation in alpha-Synuclein Membrane Association and Aggregation in Yeasts
Parkinson's disease, v 2011, p12
01 Jan 2011
PMID: 21826257
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In Parkinson's disease (PD), misfolded and aggregated alpha-synuclein protein accumulates in degenerating midbrain dopaminergic neurons. The amino acid alanine-76 in alpha-synuclein and phosphorylation at serine-87 and serine-129 are thought to regulate its aggregation and toxicity. However, their exact contributions to alpha-synuclein membrane association are less clear. We found that alpha-synuclein is indeed phosphorylated in fission yeast and budding yeast, the two models that we employed for assessing alpha-synuclein aggregation and membrane association properties, respectively. Surprisingly, blocking serine phosphorylation (S87A, S129A, and S87A/S129A) or mimicking it (S87D, S129D) altered alpha-synuclein aggregation in fission yeast. Either blocking or mimicking this phosphorylation increased endomembrane association in fission yeast, but only mimicking it decreased plasma membrane association in budding yeast. Polar substitution mutations of alanine-76 (A76E and A76R) decreased alpha-synuclein membrane association in budding yeast and decreased aggregation in fission yeast. These yeast studies extend our understanding of serine phosphorylation and alanine-76 contributions to alpha-synuclein aggregation and are the first to detail their impact on alpha-synuclein's plasma membrane and endomembrane association.
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Details
- Title
- Contribution of Alanine-76 and Serine Phosphorylation in alpha-Synuclein Membrane Association and Aggregation in Yeasts
- Creators
- Michael Fiske - Lake Forest CollegeStephanie Valtierra - Lake Forest CollegeKeith Solvang - Lake Forest CollegeMichael Zorniak - Lake Forest CollegeMichael White - Lake Forest Coll, Dept Biol, Lake Forest, IL 60045 USASara Herrera - Lake Forest CollegeAlina Konnikova - Lake Forest CollegeRebecca Brezinsky - Lake Forest CollegeShubhik DebBurman - Lake Forest College
- Publication Details
- Parkinson's disease, v 2011, p12
- Publisher
- Hindawi Publishing Group
- Number of pages
- 12
- Grant note
- Parkinson's Disease Foundation summer undergraduate research fellowship NIH-NINDS diversity supplement undergraduate research grant CCLI 0310627; MRI 0115919 / NSF; National Science Foundation (NSF) NS048508-01; NS048508-02 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NIH ARRA summer undergraduate research supplement; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000208765600031
- Scopus ID
- 2-s2.0-80052722040
- Other Identifier
- 991020837745404721
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- Web of Science research areas
- Clinical Neurology