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dc.contributor.authorClayton, Emma L
dc.contributor.authorSue, Nancy
dc.contributor.authorSmillie, Karen J
dc.contributor.authorO'Leary, Timothy
dc.contributor.authorBache, Nicolai
dc.contributor.authorCheung, Giselle
dc.contributor.authorCole, Adam R
dc.contributor.authorWyllie, David J
dc.contributor.authorSutherland, Calum
dc.contributor.authorRobinson, Phillip J
dc.contributor.authorCousin, Michael A
dc.date.accessioned2020-07-16T23:30:18Z
dc.date.available2020-07-16T23:30:18Z
dc.date.issued2010-07
dc.identifier.issn1097-6256
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/308025
dc.description.abstractGlycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.subjectCerebellum
dc.subjectHippocampus
dc.subjectNeurons
dc.subjectPresynaptic Terminals
dc.subjectSynaptic Vesicles
dc.subjectCells, Cultured
dc.subjectAnimals
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectDynamin I
dc.subjectGlycogen Synthase Kinase 3
dc.subjectSignal Transduction
dc.subjectEndocytosis
dc.subjectPhosphorylation
dc.subjectMale
dc.subjectCyclin-Dependent Kinase 5
dc.subjectIn Vitro Techniques
dc.titleDynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.
dc.typeArticle
prism.endingPage851
prism.issueIdentifier7
prism.publicationDate2010
prism.publicationNameNat Neurosci
prism.startingPage845
prism.volume13
dc.identifier.doi10.17863/CAM.55120
dcterms.dateAccepted2010-05-06
rioxxterms.versionofrecord10.1038/nn.2571
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2010-07
dc.contributor.orcidO'Leary, Timothy [0000-0002-1029-0158]
dc.identifier.eissn1546-1726
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (080066/Z/06/Z)
cam.issuedOnline2010-06-06
rioxxterms.freetoread.startdate2011-01-31


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