{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:28:16Z","timestamp":1790573296058,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS078165"],"award-info":[{"award-number":["R01NS078165"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS078165-S1"],"award-info":[{"award-number":["R01NS078165-S1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U54-NS110435"],"award-info":[{"award-number":["U54-NS110435"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01-NS109209"],"award-info":[{"award-number":["R01-NS109209"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21-NS107950"],"award-info":[{"award-number":["R21-NS107950"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01NS078165"],"award-info":[{"award-number":["R01NS078165"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01NS078165-S1"],"award-info":[{"award-number":["R01NS078165-S1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson\u2019s Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013301","name":"Parkinson\u2019s Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006049","name":"Marine Biological Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002243","name":"Alzheimer\u2019s Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\u03b1-Synuclein is a presynaptic protein that regulates synaptic vesicle trafficking under physiological conditions. However, in several neurodegenerative diseases, including Parkinson\u2019s disease, dementia with Lewy bodies, and multiple system atrophy, \u03b1-synuclein accumulates throughout the neuron, including at synapses, leading to altered synaptic function, neurotoxicity, and motor, cognitive, and autonomic dysfunction. Neurons typically contain both monomeric and multimeric forms of \u03b1-synuclein, and it is generally accepted that disrupting the balance between them promotes aggregation and neurotoxicity. However, it remains unclear how distinct molecular species of \u03b1-synuclein affect synapses where \u03b1-synuclein is normally expressed. Using the lamprey reticulospinal synapse model, we previously showed that acute introduction of excess recombinant monomeric or dimeric \u03b1-synuclein impaired distinct stages of clathrin-mediated synaptic vesicle endocytosis, leading to a loss of synaptic vesicles. Here, we expand this knowledge by investigating the effects of native, physiological \u03b1-synuclein isolated from the brain of a neuropathologically normal human subject, which comprised predominantly helically folded multimeric \u03b1-synuclein with a minor component of monomeric \u03b1-synuclein. After acute introduction of excess brain-derived human \u03b1-synuclein, there was a moderate reduction in the synaptic vesicle cluster and an increase in the number of large, atypical vesicles called \u201ccisternae.\u201d In addition, brain-derived \u03b1-synuclein increased synaptic vesicle and cisternae sizes and induced atypical fusion\/fission events at the active zone. In contrast to monomeric or dimeric \u03b1-synuclein, the brain-derived multimeric \u03b1-synuclein did not appear to alter clathrin-mediated synaptic vesicle endocytosis. Taken together, these data suggest that excess brain-derived human \u03b1-synuclein impairs intracellular vesicle trafficking and further corroborate the idea that different molecular species of \u03b1-synuclein produce distinct trafficking defects at synapses. These findings provide insights into the mechanisms by which excess \u03b1-synuclein contributes to synaptic deficits and disease phenotypes.<\/jats:p>","DOI":"10.3389\/fnins.2021.639414","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T07:48:58Z","timestamp":1612424938000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of Excess Brain-Derived Human \u03b1-Synuclein on Synaptic Vesicle Trafficking"],"prefix":"10.3389","volume":"15","author":[{"given":"Cristina","family":"Rom\u00e1n-Vendrell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey T.","family":"Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Sanderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Bartels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11116","DOI":"10.1073\/pnas.1903054116","article-title":"Synapsins regulate \u03b1-synuclein functions.","volume":"116","author":"Atias","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0448-19.2020","article-title":"Hsc70 ameliorates the vesicle recycling defects caused by excess alpha-synuclein at synapses.","volume":"7","author":"Banks","year":"2020","journal-title":"eNeuro"},{"key":"B3","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nature10324","article-title":"\u03b1-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation.","volume":"477","author":"Bartels","year":"2011","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116473","article-title":"Identification of synaptosomal proteins binding to monomeric and oligomeric \u03b1-synuclein.","volume":"10","author":"Betzer","year":"2015","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1523\/JNEUROSCI.2898-12.2013","article-title":"Mapping the subcellular distribution of alpha-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: implications for Parkinson\u2019s disease pathogenesis.","volume":"33","author":"Boassa","year":"2013","journal-title":"J. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1111\/jnc.14965","article-title":"Synucleinopathies: where we are and where we need to go.","volume":"153","author":"Br\u00e1s","year":"2020","journal-title":"J. Neurochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1093\/hmg\/ddu521","article-title":"Rab11 modulates alpha-synuclein-mediated defects in synaptic transmission and behaviour.","volume":"24","author":"Breda","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"E4274","DOI":"10.1073\/pnas.1416598111","article-title":"\u03b1-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation.","volume":"111","author":"Burr\u00e9","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024091","article-title":"Cell biology and pathophysiology of alpha-synuclein.","volume":"8","author":"Burr\u00e9","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1126\/science.1195227","article-title":"\u03b1-synuclein promotes SNARE-complex assembly in Vivo and in Vitro.","volume":"329","author":"Burre","year":"2010","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3926","DOI":"10.1091\/mbc.E14-02-0708","article-title":"Acute increase of alpha-synuclein inhibits synaptic vesicle recycling evoked during intense stimulation.","volume":"25","author":"Busch","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"8209","DOI":"10.1523\/jneurosci.1158-19.2019","article-title":"The synaptic vesicle cycle revisited: new insights into the modes and mechanisms.","volume":"39","author":"Chanaday","year":"2019","journal-title":"J. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"15313","DOI":"10.1074\/jbc.M213128200","article-title":"A broken alpha -helix in folded alpha -synuclein.","volume":"278","author":"Chandra","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1083\/jcb.150.4.839","article-title":"Differential regulation of granule-to-granule and granule-to-plasma membrane fusion during secretion from rat pituitary lactotrophs.","volume":"150","author":"Cochilla","year":"2000","journal-title":"J. Cell Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"9443","DOI":"10.1074\/jbc.273.16.9443","article-title":"Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes.","volume":"273","author":"Davidson","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"6371","DOI":"10.1074\/jbc.m112.403311","article-title":"In vivocross-linking reveals principally oligomeric forms of \u03b1-synuclein and \u03b2-synuclein in neurons and non-neural cells.","volume":"288","author":"Dettmer","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8314","article-title":"Parkinson-causing alpha-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation.","volume":"6","author":"Dettmer","year":"","journal-title":"Nat. Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"9596","DOI":"10.1073\/pnas.1505953112","article-title":"KTKEGV repeat motifs are key mediators of normal alpha-synuclein tetramerization: their mutation causes excess monomers and neurotoxicity.","volume":"112","author":"Dettmer","year":"","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3466","DOI":"10.1093\/hmg\/ddx227","article-title":"Loss of native alpha-synuclein multimerization by strategically mutating its amphipathic helix causes abnormal vesicle interactions in neuronal cells.","volume":"26","author":"Dettmer","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/nature05185","article-title":"Phosphoinositides in cell regulation and membrane dynamics.","volume":"443","author":"Di Paolo","year":"2006","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/elife.00592","article-title":"Native \u03b1-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2\/VAMP2.","volume":"2","author":"Diao","year":"2013","journal-title":"Elife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6043","DOI":"10.1523\/JNEUROSCI.0179-17.2017","article-title":"Wild-type monomeric alpha-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held.","volume":"37","author":"Eguchi","year":"2017","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s00109-013-1038-9","article-title":"alpha-Synuclein and intracellular trafficking: impact on the spreading of Parkinson\u2019s disease pathology.","volume":"91","author":"Eisbach","year":"2013","journal-title":"J. Mol. Med."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-019-0103-7","article-title":"Parkinson\u2019s disease: proteinopathy or lipidopathy?","volume":"6","author":"Fanning","year":"2020","journal-title":"npj Parkinsons Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/j.1365-2818.2005.01466.x","article-title":"Reconstruct: a free editor for serial section microscopy.","volume":"218","author":"Fiala","year":"2005","journal-title":"J. Microsc."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12563","article-title":"Structural basis of synaptic vesicle assembly promoted by \u03b1-synuclein.","volume":"7","author":"Fusco","year":"2016","journal-title":"Nat. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/s0896-6273(00)00038-6","article-title":"Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the sh3 domain of endophilin.","volume":"27","author":"Gad","year":"2000","journal-title":"Neuron"},{"key":"B28","doi-asserted-by":"publisher","first-page":"7929","DOI":"10.1074\/jbc.c113.538249","article-title":"Evidence of native \u03b1-synuclein conformers in the human brain.","volume":"289","author":"Gould","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134316","article-title":"\u03b1-Synuclein pathology in Parkinson\u2019s disease and related \u03b1-synucleinopathies.","volume":"709","author":"Henderson","year":"2019","journal-title":"Neurosci. Lett."},{"key":"B30","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.tins.2014.12.009","article-title":"Impaired intracellular trafficking defines early Parkinson\u2019s disease.","volume":"38","author":"Hunn","year":"2015","journal-title":"Trends Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1073\/pnas.1700465115","article-title":"GBA1 deficiency negatively affects physiological \u03b1-synuclein tetramers and related multimers.","volume":"115","author":"Kim","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1523\/jneurosci.4564-06.2007","article-title":"Presynaptic -synuclein aggregates, Not lewy bodies, cause neurodegeneration in dementia with lewy bodies.","volume":"27","author":"Kramer","year":"2007","journal-title":"J. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nn.4529","article-title":"\u03b1-Synuclein promotes dilation of the exocytotic fusion pore.","volume":"20","author":"Logan","year":"2017","journal-title":"Nat. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1021\/bi501188a","article-title":"Purification of \u03b1-synuclein from human brain reveals an instability of endogenous multimers as the protein approaches purity.","volume":"54","author":"Luth","year":"2015","journal-title":"Biochemistry"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00018","article-title":"A role of cholesterol in modulating the binding of \u03b1-synuclein to synaptic-like vesicles.","volume":"14","author":"Man","year":"2020","journal-title":"Front. Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2804","DOI":"10.1523\/jneurosci.08-08-02804.1988","article-title":"Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal.","volume":"8","author":"Maroteaux","year":"1988","journal-title":"J. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"5403","DOI":"10.1523\/jneurosci.0935-08.2008","article-title":"Evidence that vesicles undergo compound fusion on the synaptic ribbon.","volume":"28","author":"Matthews","year":"2008","journal-title":"J. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"647","DOI":"10.4103\/1673-5374.230289","article-title":"Impacts of increased alpha-synuclein on clathrin-mediated endocytosis at synapses: implications for neurodegenerative diseases.","volume":"13","author":"Medeiros","year":"2018","journal-title":"Neural. Regen. Res."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00388","article-title":"alpha-synuclein dimers impair vesicle fission during clathrin-mediated synaptic vesicle recycling.","volume":"11","author":"Medeiros","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"10201","DOI":"10.1523\/jneurosci.19-23-10201.1999","article-title":"A role for the clathrin assembly domain of ap180 in synaptic vesicle endocytosis.","volume":"19","author":"Morgan","year":"1999","journal-title":"J. Neurosci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3214","DOI":"10.1523\/jneurosci.20-09-03214.2000","article-title":"Synucleins are developmentally expressed, and \u03b1-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons.","volume":"20","author":"Murphy","year":"2000","journal-title":"J. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.neuron.2009.12.023","article-title":"Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis.","volume":"65","author":"Nemani","year":"2010","journal-title":"Neuron"},{"key":"B43","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.neuron.2018.09.014","article-title":"Abrogating native alpha-synuclein tetramers in mice causes a L-DOPA-responsive motor syndrome closely resembling Parkinson\u2019s disease.","volume":"100","author":"Nuber","year":"2018","journal-title":"Neuron"},{"key":"B44","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1083\/jcb.201011118","article-title":"\u03b1-Synuclein and ALPS motifs are membrane curvature sensors whose contrasting chemistry mediates selective vesicle binding.","volume":"194","author":"Pranke","year":"2011","journal-title":"J. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s00401-010-0711-0","article-title":"The synaptic pathology of alpha-synuclein aggregation in dementia with lewy bodies. Parkinson\u2019s disease and Parkinson\u2019s disease dementia.","volume":"120","author":"Schulz-Schaeffer","year":"2010","journal-title":"Acta Neuropathol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"8083","DOI":"10.1523\/JNEUROSCI.1091-10.2010","article-title":"A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration.","volume":"30","author":"Scott","year":"2010","journal-title":"J. Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.cell.2018.02.062","article-title":"Visualization of membrane pore in live cells reveals a dynamic-pore theory governing fusion and endocytosis.","volume":"173","author":"Shin","year":"2018","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1126\/science.276.5310.259","article-title":"Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions.","volume":"276","author":"Shupliakov","year":"1997","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00405","article-title":"\u03b1-Synuclein-112 impairs Synaptic vesicle recycling consistent with Its enhanced membrane binding properties.","volume":"8","author":"Soll","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1749-6632.2000.tb06900.x","article-title":"The alpha-synucleinopathies: Parkinson\u2019s disease, dementia with lewy bodies, and multiple system atrophy.","volume":"920","author":"Spillantini","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1523\/JNEUROSCI.2581-13.2014","article-title":"Presynaptic alpha-synuclein aggregation in a mouse model of Parkinson\u2019s disease.","volume":"34","author":"Spinelli","year":"2014","journal-title":"J. Neurosci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/jnc.14810","article-title":"The physiological role of \u03b1-synuclein and its relationship to Parkinson\u2019s Disease.","volume":"150","author":"Sulzer","year":"2019","journal-title":"J. Neurochem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1242\/jcs.072686","article-title":"An endophilin-dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling.","author":"Sundborger","year":"2011","journal-title":"J. Cell Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1177\/1073858412461691","article-title":"Fusion pores, SNAREs, and exocytosis.","volume":"19","author":"Vardjan","year":"2013","journal-title":"Neuroscientist"},{"key":"B55","doi-asserted-by":"publisher","first-page":"9364","DOI":"10.1523\/JNEUROSCI.4787-13.2014","article-title":"Synucleins regulate the kinetics of synaptic vesicle endocytosis.","volume":"34","author":"Vargas","year":"2014","journal-title":"J. Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.celrep.2016.12.023","article-title":"Synucleins have multiple effects on presynaptic architecture.","volume":"18","author":"Vargas","year":"2017","journal-title":"Cell Rep."},{"key":"B57","doi-asserted-by":"publisher","first-page":"32486","DOI":"10.1074\/jbc.m110.139576","article-title":"Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins.","volume":"285","author":"Varkey","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"4010","DOI":"10.1091\/mbc.E14-02-0741","article-title":"Formation of alpha-synuclein Lewy neurite-like aggregates in axons impedes the transport of distinct endosomes.","volume":"25","author":"Volpicelli-Daley","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/978-1-4939-8719-1_6","article-title":"Acute manipulations of clathrin-mediated endocytosis at presynaptic nerve terminals.","volume":"1847","author":"Walsh","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"17797","DOI":"10.1073\/pnas.1113260108","article-title":"A soluble -synuclein construct forms a dynamic tetramer.","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1074\/jbc.M112.418871","article-title":"Monomeric synucleins generate membrane curvature.","volume":"288","author":"Westphal","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B62","doi-asserted-by":"publisher","first-page":"4408","DOI":"10.1523\/JNEUROSCI.3627-15.2016","article-title":"alpha-synuclein mutation inhibits endocytosis at mammalian central nerve terminals.","volume":"36","author":"Xu","year":"2016","journal-title":"J. Neurosci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"12036","DOI":"10.1039\/c9cp02464f","article-title":"On the ubiquity of helical \u03b1-synuclein tetramers.","volume":"21","author":"Xu","year":"2019","journal-title":"Phys. Chem. Chem. Phys."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1016\/s0896-6273(00)80664-9","article-title":"Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis.","volume":"21","author":"Zhang","year":"1998","journal-title":"Neuron"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.639414\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T07:49:02Z","timestamp":1612424942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.639414\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":64,"alternative-id":["10.3389\/fnins.2021.639414"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2021.639414","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]},"article-number":"639414"}}