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dc.contributor.authorLautenschläger, Janin
dc.contributor.authorStephens, Amberley D
dc.contributor.authorFusco, Giuliana
dc.contributor.authorStröhl, Florian
dc.contributor.authorCurry, Nathan
dc.contributor.authorZacharopoulou, Maria
dc.contributor.authorMichel, Claire H
dc.contributor.authorLaine, Romain
dc.contributor.authorNespovitaya, Nadezhda
dc.contributor.authorFantham, Marcus
dc.contributor.authorPinotsi, Dorothea
dc.contributor.authorZago, Wagner
dc.contributor.authorFraser, Paul
dc.contributor.authorTandon, Anurag
dc.contributor.authorSt George-Hyslop, Peter
dc.contributor.authorRees, Eric
dc.contributor.authorPhillips, Jonathan J
dc.contributor.authorDe Simone, Alfonso
dc.contributor.authorKaminski, Clemens F
dc.contributor.authorSchierle, Gabriele S Kaminski
dc.date.accessioned2018-07-31T13:46:51Z
dc.date.available2018-07-31T13:46:51Z
dc.date.issued2018-02-19
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/278584
dc.description.abstractAlpha-synuclein is known to bind to small unilamellar vesicles (SUVs) via its N terminus, which forms an amphipathic alpha-helix upon membrane interaction. Here we show that calcium binds to the C terminus of alpha-synuclein, therewith increasing its lipid-binding capacity. Using CEST-NMR, we reveal that alpha-synuclein interacts with isolated synaptic vesicles with two regions, the N terminus, already known from studies on SUVs, and additionally via its C terminus, which is regulated by the binding of calcium. Indeed, dSTORM on synaptosomes shows that calcium mediates the localization of alpha-synuclein at the pre-synaptic terminal, and an imbalance in calcium or alpha-synuclein can cause synaptic vesicle clustering, as seen ex vivo and in vitro. This study provides a new view on the binding of alpha-synuclein to synaptic vesicles, which might also affect our understanding of synucleinopathies.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPresynaptic Terminals
dc.subjectSynaptic Vesicles
dc.subjectCell Line
dc.subjectSynaptosomes
dc.subjectAnimals
dc.subjectHumans
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectCalcium
dc.subjectMicroscopy, Electron, Transmission
dc.subjectNuclear Magnetic Resonance, Biomolecular
dc.subjectBinding Sites
dc.subjectProtein Binding
dc.subjectLipid Metabolism
dc.subjectalpha-Synuclein
dc.subjectIn Vitro Techniques
dc.subjectProtein Aggregates
dc.titleC-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameNat Commun
prism.startingPage712
prism.volume9
dc.identifier.doi10.17863/CAM.25919
dcterms.dateAccepted2018-01-19
rioxxterms.versionofrecord10.1038/s41467-018-03111-4
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-02-19
dc.contributor.orcidStephens, Amberley D [0000-0002-7303-6392]
dc.contributor.orcidStröhl, Florian [0000-0002-2603-0780]
dc.contributor.orcidSt George-Hyslop, Peter [0000-0003-0796-7209]
dc.contributor.orcidPhillips, Jonathan J [0000-0002-5361-9582]
dc.contributor.orcidKaminski, Clemens F [0000-0002-5194-0962]
dc.contributor.orcidSchierle, Gabriele S Kaminski [0000-0002-1843-2202]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/K02292X/1)
pubs.funder-project-idAlzheimer's Research UK (ARUK-PG2013-14)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/H023917/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/H018301/1)
pubs.funder-project-idMedical Research Council (G0902243)
pubs.funder-project-idWellcome Trust (203249/Z/16/Z)
cam.issuedOnline2018-02-19


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International