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dc.contributor.authorGoggolidou, Paraskevi
dc.contributor.authorStevens, Jonathan L
dc.contributor.authorAgueci, Francesco
dc.contributor.authorKeynton, Jennifer
dc.contributor.authorWheway, Gabrielle
dc.contributor.authorGrimes, Daniel T
dc.contributor.authorPatel, Saloni H
dc.contributor.authorHilton, Helen
dc.contributor.authorMorthorst, Stine K
dc.contributor.authorDiPaolo, Antonella
dc.contributor.authorWilliams, Debbie J
dc.contributor.authorSanderson, Jeremy
dc.contributor.authorKhoronenkova, Svetlana V
dc.contributor.authorPowles-Glover, Nicola
dc.contributor.authorErmakov, Alexander
dc.contributor.authorEsapa, Chris T
dc.contributor.authorRomero, Rosario
dc.contributor.authorDianov, Grigory L
dc.contributor.authorBriscoe, James
dc.contributor.authorJohnson, Colin A
dc.contributor.authorPedersen, Lotte B
dc.contributor.authorNorris, Dominic P
dc.date.accessioned2018-10-23T14:35:44Z
dc.date.available2018-10-23T14:35:44Z
dc.date.issued2014-10-07
dc.identifier.pmid25294941
dc.identifier.doi10.1242/dev.107755
dc.identifier.urihttp://hdl.handle.net/2436/621803
dc.description.abstractInitially identified in DNA damage repair, ATM-interactor (ATMIN) further functions as a transcriptional regulator of lung morphogenesis. Here we analyse three mouse mutants, Atmin(gpg6/gpg6), Atmin(H210Q/H210Q) and Dynll1(GT/GT), revealing how ATMIN and its transcriptional target dynein light chain LC8-type 1 (DYNLL1) are required for normal lung morphogenesis and ciliogenesis. Expression screening of ciliogenic genes confirmed Dynll1 to be controlled by ATMIN and further revealed moderately altered expression of known intraflagellar transport (IFT) protein-encoding loci in Atmin mutant embryos. Significantly, Dynll1(GT/GT) embryonic cilia exhibited shortening and bulging, highly similar to the characterised retrograde IFT phenotype of Dync2h1. Depletion of ATMIN or DYNLL1 in cultured cells recapitulated the in vivo ciliogenesis phenotypes and expression of DYNLL1 or the related DYNLL2 rescued the effects of loss of ATMIN, demonstrating that ATMIN primarily promotes ciliogenesis by regulating Dynll1 expression. Furthermore, DYNLL1 as well as DYNLL2 localised to cilia in puncta, consistent with IFT particles, and physically interacted with WDR34, a mammalian homologue of the Chlamydomonas cytoplasmic dynein 2 intermediate chain that also localised to the cilium. This study extends the established Atmin-Dynll1 relationship into a developmental and a ciliary context, uncovering a novel series of interactions between DYNLL1, WDR34 and ATMIN. This identifies potential novel components of cytoplasmic dynein 2 and furthermore provides fresh insights into the molecular pathogenesis of human skeletal ciliopathies.
dc.description.sponsorshipMedical Research Council
dc.language.isoen
dc.publisherCompany of Biologists
dc.relation.urlhttp://dev.biologists.org/content/141/20/3966
dc.subjectAsciz
dc.subjectAtmin
dc.subjectCiliogenesis
dc.subjectCiliopathy
dc.subjectDynll1
dc.subjectMouse
dc.subjectCilia
dc.titleATMIN is a transcriptional regulator of both lung morphogenesis and ciliogenesis
dc.typeJournal article
dc.identifier.journalDevelopment
dc.date.accepted2014-08-20
rioxxterms.funderPKD Charity UK, and the Faculty of Science and Engineering, University of Wolverhampton central funding, Medical Research Council
rioxxterms.identifier.projectUOW23102018PG
rioxxterms.versionNA
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2014-10-04
dc.source.journaltitleDevelopment (Cambridge, England)
refterms.dateFOA2020-04-30T11:30:50Z


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