ArticleThe Journal of biological chemistry2015
Parkinson disease mutant E46K enhances α-synuclein phosphorylation in mammalian cell lines, in yeast, and in vivo.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 65 citations in OpenAlex.
- Genetics of α-Synuclein: The Prime Pathological Player of Parkinson's Disease.Neurotoxicity research · 2026Review
- Genes near tRNAs are enriched in translational machinery.G3 (Bethesda, Md.) · 2026Article
- Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genes near tRNAs are enriched in translational machinery.bioRxiv : the preprint server for biology · 2026Article
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Structural and functional insights into the nuclear role of Parkinson's disease-associated α-synuclein as a histone chaperone.Communications biology · 2025Article
- Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease.Cell reports · 2025Article
- CRBN modulates synuclein fibrillation via degradation of DNAJB1 in mouse model of Parkinson disease.NPJ Parkinson's disease · 2024Article
- Article
- Tumor necrosis factor mediates USE1-independent FAT10ylation under inflammatory conditions.Life science alliance · 2023Article
- Palmitoylation of the Parkinson's disease-associated protein synaptotagmin-11 links its turnover to α-synuclein homeostasis.Science signaling · 2023Article
- Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.NPJ Parkinson's disease · 2022Article
- Synuclein Analysis in AdultInternational journal of molecular sciences · 2022Article
- Kisspeptin-10 Rescues Cholinergic Differentiated SHSY-5Y Cells from α-Synuclein-Induced Toxicity In Vitro.International journal of molecular sciences · 2022Article
- A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity.Science advances · 2022Article
- CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders.Frontiers in molecular biosciences · 2022Review
- The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Aggregates.Journal of neuropathology and experimental neurology · 2021Review
- Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get.Journal of neurochemistry · 2021Article
- Dietary Polyphenols in Metabolic and Neurodegenerative Diseases: Molecular Targets in Autophagy and Biological Effects.Antioxidants (Basel, Switzerland) · 2021Review
- Effects of Detergent on α-Synuclein Structure. A Native MS-Ion Mobility Study.International journal of molecular sciences · 2020Article
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Although α-synuclein (α-syn) phosphorylation has been considered as a hallmark of sporadic and familial Parkinson disease (PD), little is known about the effect of PD-linked mutations on α-syn phosphorylation. In this study, we investigated the effects of the A30P, E46K, and A53T PD-linked mutations on α-syn phosphorylation at residues Ser-87 and Ser-129. Although the A30P and A53T mutants slightly affected Ser(P)-129 levels compared with WT α-syn, the E46K mutation significantly enhanced Ser-129 phosphorylation in yeast and mammalian cell lines. This effect was not due to the E46K mutant being a better kinase substrate nor due to alterations in endogenous kinase levels, but was mostly linked with enhanced nuclear and endoplasmic reticulum accumulation. Importantly, lentivirus-mediated overexpression in mice also showed enhanced Ser-129 phosphorylation of the E46K mutant compared to WT α-syn, thus providing in vivo validation of our findings. Altogether, our findings suggest that the different PD-linked mutations may contribute to PD pathogenesis via different mechanisms.
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