ArticlePloS one2018
Ubiquitination of alpha-synuclein filaments by Nedd4 ligases.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Article
- Single-cell spatial proteomic imaging for human neuropathology.Acta neuropathologica communications · 2022Article
- Review
- Small Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.ACS chemical neuroscience · 2021Article
- Review
- Deletion of ubiquitin ligase Nedd4l exacerbates ischemic brain damage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective.Cell death and differentiation · 2021Review
- Characterization of Small-Molecule-Induced Changes in Parkinson's-Related Trafficking via the Nedd4 Ubiquitin Signaling Cascade.Cell chemical biology · 2021Article
- Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.PloS one · 2021Article
- Robust and facile purification of full-length, untagged human Nedd4 as a recombinant protein from Escherichia coli.Protein expression and purification · 2020Article
- Basic Fibroblast Growth Factor 2-Induced Proteome Changes Endorse Lewy Body Pathology in Hippocampal Neurons.iScience · 2020Article
- Protein-Protein Interactions in Alpha-Synuclein Biogenesis: New Potential Targets in Parkinson's Disease.Frontiers in aging neuroscience · 2020Article
- Post-translational modification and protein sorting to small extracellular vesicles including exosomes by ubiquitin and UBLs.Cellular and molecular life sciences : CMLS · 2019Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Alpha-synuclein can form beta-sheet filaments, the accumulation of which plays a key role in the development of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. It has previously been shown that alpha-synuclein is a substrate for the HECT domain-containing ubiquitin ligase Nedd4, and is subject to ubiquitin-mediated endosomal degradation. We show here that alpha-synuclein filaments are much better substrates for ubiquitination in vitro than monomeric alpha-synuclein, and that this increased susceptibility cannot be mimicked by the mere clustering of monomers. Recognition by Nedd4 family enzymes is not through the conventional binding of PPxY-containing sequences to WW domains of the ligase, but it also involves C2 and HECT domains. The disease-causing alpha-synuclein mutant A53T is a much less efficient substrate for Nedd4 ligases than the wild-type protein. We suggest that preferential recognition, ubiquitination and degradation of beta-sheet-containing filaments may help to limit toxicity, and that A53T alpha-synuclein may be more toxic, at least in part because it avoids this fate.
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Registered trials
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.