ArticleScientific reports2016
A genome-wide imaging-based screening to identify genes involved in synphilin-1 inclusion formation in Saccharomyces cerevisiae.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 23 citations in OpenAlex.
- Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids.eLife · 2025Article
- Single-cell image analysis to explore cell-to-cell heterogeneity in isogenic populations.Cell systems · 2021Review
- TheCellVision.org: A Database for Visualizing and Mining High-Content Cell Imaging Projects.G3 (Bethesda, Md.) · 2020Article
- Perturbing proteomes at single residue resolution using base editing.Nature communications · 2020Article
- FMN reduces Amyloid-β toxicity in yeast by regulating redox status and cellular metabolism.Nature communications · 2020Article
- Recent Insights on Alzheimer's Disease Originating from Yeast Models.International journal of molecular sciences · 2018Review
- Review
- Restricted access: spatial sequestration of damaged proteins during stress and aging.EMBO reports · 2017Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synphilin-1 is a major component of Parkinson's disease (PD) inclusion bodies implicated in PD pathogenesis. However, the machinery controlling synphilin-1 inclusion formation remains unclear. Here, we investigated synphilin-1 inclusion formation using a systematic genome-wide, high-content imaging based screening approach (HCI) in the yeast Saccharomyces cerevisiae. By combining with a secondary screening for mutants showing significant changes on fluorescence signal intensity, we filtered out hits that significantly decreased the expression level of synphilin-1. We found 133 yeast genes that didn't affect synphilin-1 expression but that were required for the formation of synphilin-1 inclusions. Functional enrichment and physical interaction network analysis revealed these genes to encode for functions involved in cytoskeleton organization, histone modification, sister chromatid segregation, glycolipid biosynthetic process, DNA repair and replication. All hits were confirmed by conventional microscopy. Complementation assays were performed with a selected group of mutants, results indicated that the observed phenotypic changes in synphilin-1 inclusion formation were directly caused by the loss of corresponding genes of the deletion mutants. Further growth assays of these mutants showed a significant synthetic sick effect upon synphilin-1 expression, which supports the hypothesis that matured inclusions represent an end stage of several events meant to protect cells against the synphilin-1 cytotoxicity.
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