ArticleMolecular biology of the cell2024
Excess phosphoserine-129 α-synuclein induces synaptic vesicle trafficking and declustering defects at a vertebrate synapse.
Article in Molecular biology of the cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Standardized clinical assessments and advanced AI-driven instruments used to evaluate neurofunctional deficits, including within biomarker based framework, in Parkinson's disease - human intelligence made vs. AI models - systematic review.Frontiers in medicine · 2025Pooled it
- RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic Code Expansion, Enzymatic Modification, and C-Terminal Labeling Enable Facile Production of Highly Modified α-Synuclein.bioRxiv : the preprint server for biology · 2026Article
- Authentic Phosphorylation of α-Synuclein at Ser129 Reveals Functional Differences Not Captured by the S129D Phosphomimetic.ACS chemical biology · 2026Article
- Dysregulation of astrocytic DNAJC6 contributes to sporadic Parkinson's disease pathogenesis.The Journal of clinical investigation · 2026Article
- RNA promotes synapsin phase separation providing a platform for local translation.bioRxiv : the preprint server for biology · 2026Article
- Unlocking Parkinson's disease: harnessing the untapped potential of fatty acid metabolism in disease pathogenesis.Frontiers in immunology · 2026Review
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Synphilin-1 modulates alpha-synuclein assembly, release and uptake.NPJ Parkinson's disease · 2025Article
- Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.The Journal of physiology · 2025Article
- Condensates of synaptic vesicles and synapsin-1 mediate actin sequestering and polymerization.The EMBO journal · 2025Article
- Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson's disease.Nature communications · 2025Article
- α-Synuclein interacts directly with AP2 and regulates its binding to synaptic membranes.The Journal of biological chemistry · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein.Science advances · 2025Article
- Condensates of synaptic vesicles and synapsin are molecular beacons for actin sequestering and polymerization.bioRxiv : the preprint server for biology · 2025Article
- Blood biomarker fingerprints in a cohort of patients with CHRNE-related congenital myasthenic syndrome.Acta neuropathologica communications · 2025Article
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Acute lipid droplet accumulation induced by the inhibition of the phospholipase DDHD2 does not affect the level, solubility, or phosphoserine-129 status of α-synuclein.Metabolic brain disease · 2025Article
- Physiological roles of α-synuclein serine-129 phosphorylation - not an oxymoron.Trends in neurosciences · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
α-Synuclein is a presynaptic protein that regulates synaptic vesicle (SV) trafficking. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), α-synuclein aberrantly accumulates throughout neurons, including at synapses. During neuronal activity, α-synuclein is reversibly phosphorylated at serine 129 (pS129). While pS129 comprises ∼4% of total α-synuclein under physiological conditions, it dramatically increases in PD and DLB brains. The impacts of excess pS129 on synaptic function are currently unknown. We show here that compared with wild-type (WT) α-synuclein, pS129 exhibits increased binding and oligomerization on synaptic membranes and enhanced vesicle "microclustering" in vitro. Moreover, when acutely injected into lamprey reticulospinal axons, excess pS129 α-synuclein robustly localized to synapses and disrupted SV trafficking in an activity-dependent manner, as assessed by ultrastructural analysis. Specifically, pS129 caused a declustering and dispersion of SVs away from the synaptic vicinity, leading to a significant loss of total synaptic membrane. Live imaging further revealed altered SV cycling, as well as microclusters of recently endocytosed SVs moving away from synapses. Thus, excess pS129 caused an activity-dependent inhibition of SV trafficking via altered vesicle clustering/reclustering. This work suggests that accumulation of pS129 at synapses in diseases like PD and DLB could have profound effects on SV dynamics.
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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 Socratic graph.