ArticleHuman molecular genetics2012
Suppression of α-synuclein toxicity and vesicle trafficking defects by phosphorylation at S129 in yeast depends on genetic context.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
- STIP1/HOP promotes the formation of cytotoxic α-synuclein oligomers.Molecular neurodegeneration advances · 2026Article
- Synphilin-1 modulates alpha-synuclein assembly, release and uptake.NPJ Parkinson's disease · 2025Article
- Article
- RXR nuclear receptor signaling modulates lipid metabolism and triggers lysosomal clearance of alpha-synuclein in neuronal models of synucleinopathy.Cellular and molecular life sciences : CMLS · 2024Article
- Role of Epigenetic Modulation in Neurodegenerative Diseases: Implications of Phytochemical Interventions.Antioxidants (Basel, Switzerland) · 2024Review
- Positron Emission Tomography with [International journal of molecular sciences · 2024Article
- Sporadic SNCA mutations A18T and A29S exhibit variable effects on protein aggregation, cell viability and oxidative stress.Molecular biology reports · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies.International journal of molecular sciences · 2022Review
- α-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Decreased Vacuolar CaFrontiers in genetics · 2020Article
- Quantitative Characterization of α-Synuclein Aggregation in Living Cells through Automated Microfluidics Feedback Control.Cell reports · 2019Article
- From Yeast to Humans: Leveraging New Approaches in Yeast to Accelerate Discovery of Therapeutic Targets for Synucleinopathies.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles.Frontiers in neuroscience · 2019Review
- Post translational changes to α-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease.Molecular neurodegeneration · 2017Review
- Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets.Pharmacological reviews · 2017Review
- PhosphorylatedParkinson's disease · 2017Review
- From the baker to the bedside: yeast models of Parkinson's disease.Microbial cell (Graz, Austria) · 2015Review
- Review
- Interplay between sumoylation and phosphorylation for protection against α-synuclein inclusions.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
The aggregation of α-synuclein (αSyn) is a neuropathologic hallmark of Parkinson's disease and other synucleinopathies. In Lewy bodies, αSyn is extensively phosphorylated, predominantly at serine 129 (S129). Recent studies in yeast have shown that, at toxic levels, αSyn disrupts Rab homeostasis, causing an initial endoplasmic reticulum-to-Golgi block that precedes a generalized trafficking collapse. However, whether αSyn phosphorylation modulates trafficking defects has not been evaluated. Here, we show that constitutive expression of αSyn in yeast impairs late-exocytic, early-endocytic and/or recycling trafficking. Although members of the casein kinase I (CKI) family phosphorylate αSyn at S129, they attenuate αSyn toxicity and trafficking defects by an S129 phosphorylation-independent mechanism. Surprisingly, phosphorylation of S129 modulates αSyn toxicity and trafficking defects in a manner strictly determined by genetic background. Abnormal endosome morphology, increased levels of the endosome marker Rab5 and co-localization of mammalian CKI with αSyn aggregates are observed in brain sections from αSyn-overexpressing mice and human synucleinopathies. Our results contribute to evidence that suggests αSyn-induced defects in endocytosis, exocytosis and/or recycling of vesicles involved in these cellular processes might contribute to the pathogenesis of synucleinopathies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.