ArticleThe Journal of biological chemistry2013
α-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 66 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 110 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Synaptic vesicle architecture modulates α-synuclein conformation and pathogenic transitions in Parkinson's disease.Bioscience reports · 2026Review
- Identification of pesticides associated with an increased risk of Parkinson's disease using a multi-screen approach.Environment international · 2026Article
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- The Rab3 family proteins in age-related neurodegeneration: unraveling molecular pathways and potential therapeutic targets.npj aging · 2025Review
- α-Synuclein Pathology in Synucleinopathies: Mechanisms, Biomarkers, and Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Parkinson's disease beyond the brain: implications for treatments.Frontiers in aging neuroscience · 2025Review
- Alpha-Synuclein and Microglia in Parkinson's Disease: From Pathogenesis to Therapeutic Prospects.Journal of clinical medicine · 2024Review
- Systematic identification of structure-specific protein-protein interactions.Molecular systems biology · 2024Article
- Excess phosphoserine-129 α-synuclein induces synaptic vesicle trafficking and declustering defects at a vertebrate synapse.Molecular biology of the cell · 2024Article
- Review
- Synucleinopathies: Intrinsic and Extrinsic Factors.Cell biochemistry and biophysics · 2023Article
- Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders.Frontiers in cellular neuroscience · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders.Frontiers in molecular neuroscience · 2023Review
- Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects.NPJ Parkinson's disease · 2022Article
- The Role of Rab Proteins in Parkinson's Disease Synaptopathy.Biomedicines · 2022Review
- Regulation of Protein Transport Pathways by the Cytosolic Hsp90s.Biomolecules · 2022Review
- NMDA and AMPA Receptors at Synapses: Novel Targets for Tau and α-Synuclein Proteinopathies.Biomedicines · 2022Review
- Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer's Disease.Biomedicines · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Correction · 2020-10-09Error in Image ·
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
α-Synuclein is an abundant presynaptic protein and a primary component of Lewy bodies in Parkinson disease. Although its pathogenic role remains unclear, in healthy nerve terminals α-synuclein undergoes a cycle of membrane binding and dissociation. An α-synuclein binding assay was used to screen for vesicle proteins involved in α-synuclein membrane interactions and showed that antibodies directed to the Ras-related GTPase Rab3a and its chaperone RabGDI abrogated α-synuclein membrane binding. Biochemical analyses, including density gradient sedimentation and co-immunoprecipitation, suggested that α-synuclein interacts with membrane-associated GTP-bound Rab3a but not to cytosolic GDP-Rab3a. Accumulation of membrane-bound α-synuclein was induced by the expression of a GTPase-deficient Rab3a mutant, by a dominant-negative GDP dissociation inhibitor mutant unable to recycle Rab3a off membranes, and by Hsp90 inhibitors, radicicol and geldanamycin, which are known to inhibit Rab3a dissociation from membranes. Thus, all treatments that inhibited Rab3a recycling also increased α-synuclein sequestration on intracellular membranes. Our results suggest that membrane-bound GTP-Rab3a stabilizes α-synuclein on synaptic vesicles and that the GDP dissociation inhibitor·Hsp90 complex that controls Rab3a membrane dissociation also regulates α-synuclein dissociation during synaptic activity.
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What OpenQuestion holds
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.