ArticleThe Journal of biological chemistry2013
Monomeric synucleins generate membrane curvature.
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. Cited by 123 papers.
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123 citing papers in PubMed, 195 citations in OpenAlex.
- Lipid membrane remodeling by myristic acid treatment reverses Parkinson's disease α-synuclein phenotypes in patient neurons.npj metabolic health and disease · 2026Article
- WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease.bioRxiv : the preprint server for biology · 2026Article
- MiR-7 in neurological disorders: beyond metabolic dysregulation.Frontiers in neuroscience · 2026Review
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.The Journal of physiology · 2025Article
- Soma-localized Rab39 inhibits synaptic autophagy by controlling trafficking of Atg9 vesicles.The EMBO journal · 2025Article
- Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice.JCI insight · 2025Article
- N-Homocysteinylation of lysine residues in α-Synuclein enhances aggregation propensity and cytotoxicity in SH-SY5Y cells.Scientific reports · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Alpha-synuclein expression in neurons modulates Japanese encephalitis virus infection.Journal of virology · 2024Article
- Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development.Metallomics : integrated biometal science · 2024Review
- Reducing the lipase LIPE in mutant α-synuclein mice improves Parkinson-like deficits and reveals sex differences in fatty acid metabolism.Neurobiology of disease · 2024Article
- Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.EMBO molecular medicine · 2024Article
- Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations.International journal of molecular sciences · 2024Review
- Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson's disease phenotypes.NPJ Parkinson's disease · 2024Article
- From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein.International journal of molecular sciences · 2024Review
- Lipids and α-Synuclein: adding further variables to the equation.Frontiers in molecular biosciences · 2024Review
- Adding hydrophobicity or positive charges to the cytosolic half of the α-synuclein 3-11 helix increases membrane association and S129 phosphorylation.FEBS letters · 2024Article
63 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
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Abstract
Synucleins are a family of presynaptic membrane binding proteins. α-Synuclein, the principal member of this family, is mutated in familial Parkinson disease. To gain insight into the molecular functions of synucleins, we performed an unbiased proteomic screen and identified synaptic protein changes in αβγ-synuclein knock-out brains. We observed increases in the levels of select membrane curvature sensing/generating proteins. One of the most prominent changes was for the N-BAR protein endophilin A1. Here we demonstrate that the levels of synucleins and endophilin A1 are reciprocally regulated and that they are functionally related. We show that all synucleins can robustly generate membrane curvature similar to endophilins. However, only monomeric but not tetrameric α-synuclein can bend membranes. Further, A30P α-synuclein, a Parkinson disease mutant that disrupts protein folding, is also deficient in this activity. This suggests that synucleins generate membrane curvature through the asymmetric insertion of their N-terminal amphipathic helix. Based on our findings, we propose to include synucleins in the class of amphipathic helix-containing proteins that sense and generate membrane curvature. These results advance our understanding of the physiological function of synucleins.
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