Show simple item record

dc.contributor.authorDzhindzhev, Nikola S
dc.contributor.authorTzolovsky, George
dc.contributor.authorLipinszki, Zoltan
dc.contributor.authorAbdelaziz, Mohammed
dc.contributor.authorDebski, Janus
dc.contributor.authorDadlez, Michal
dc.contributor.authorGlover, David M
dc.date.accessioned2018-04-20T14:07:43Z
dc.date.available2018-04-20T14:07:43Z
dc.date.issued2017-12
dc.identifier.issn2046-2441
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275079
dc.description.abstractThe conserved process of centriole duplication requires Plk4 kinase to recruit and promote interactions between Sas6 and Sas5/Ana2/STIL (respective nomenclature of worms/flies/humans). Plk4-mediated phosphorylation of Ana2/STIL in its conserved STAN motif has been shown to promote its interaction with Sas6. However, STAN motif phosphorylation is not required for recruitment of Ana2 to the centriole. Here we show that in Drosophila, Ana2 loads onto the site of procentriole formation ahead of Sas6 in a process that also requires Plk4. However, whereas Plk4 is first recruited to multiple sites around the ring of zone II at the periphery of the centriole, Ana2 is recruited to a single site in telophase before Plk4 becomes finally restricted to this same single site. When we over-ride the auto-destruction of Plk4, it remains localized to multiple sites in the outer ring of the centriole and, if catalytically active, recruits Ana2 to these sites. Thus, it is the active form of Plk4 that promotes Ana2's recruitment to the centriole. We now show that Plk4 phosphorylates Ana2 at a site other than the STAN motif, which lies in a conserved region we term the ANST (ANa2-STil) motif. Mutation of this site, S38, to a non-phosphorylatable residue prevents the procentriole loading of Ana2 and blocks centriole duplication. Thus the initiation of procentriole formation requires Plk4 to first phosphorylate a single serine residue in the ANST motif to promote Ana2's recruitment and, secondly, to phosphorylate four residues in the STAN motif enabling Ana2 to recruit Sas6. We discuss these findings in light of the multiple Plk4 phosphorylation sites on Ana2.
dc.format.mediumPrint
dc.languageeng
dc.publisherThe Royal Society
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line
dc.subjectCentrioles
dc.subjectAnimals
dc.subjectDrosophila melanogaster
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectCell Cycle Proteins
dc.subjectMicrotubule-Associated Proteins
dc.subjectDrosophila Proteins
dc.subjectProtein Processing, Post-Translational
dc.subjectPhosphorylation
dc.titleTwo-step phosphorylation of Ana2 by Plk4 is required for the sequential loading of Ana2 and Sas6 to initiate procentriole formation.
dc.typeArticle
prism.issueIdentifier12
prism.publicationDate2017
prism.publicationNameOpen Biol
prism.volume7
dc.identifier.doi10.17863/CAM.22259
dcterms.dateAccepted2017-11-29
rioxxterms.versionofrecord10.1098/rsob.170247
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-12
dc.contributor.orcidGlover, David M [0000-0003-0956-0103]
dc.identifier.eissn2046-2441
rioxxterms.typeJournal Article/Review
cam.issuedOnline2017-12-20


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

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