Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization

dc.contributor.authorCullilane, Andrew Robert
dc.contributor.authorStraatman-Iwanowska, Anna A.
dc.contributor.authorZaucker, Andreas
dc.contributor.authorWakabayashi, Yoshiyuki
dc.contributor.authorBruce, Christopher K.
dc.contributor.authorLuo, Guanmei
dc.contributor.authorRahman, Fatimah
dc.contributor.authorGürakan, Figen
dc.contributor.authorÜtine, Gülen Eda
dc.contributor.authorDenecke, Jonas
dc.contributor.authorVukovic, Jurica
dc.contributor.authorDi Rocco, Maja
dc.contributor.authorMandel, Hanna
dc.contributor.authorMatthews, Randolph P.
dc.contributor.authorThomas, Steven G.
dc.contributor.authorRappoport, Joshua Zachary
dc.contributor.authorArias, Irwin M.
dc.contributor.authorWolburg, Hartwig
dc.contributor.authorKnisely, Alexander S.
dc.contributor.authorKelly, Deirdre Anne K.
dc.contributor.authorFerenc Müller, Ferenc
dc.contributor.authorMäher, Eamonn Richard
dc.contributor.authorGissen, Paul
dc.contributor.buuauthorÖzkan, Tanju Başarır
dc.contributor.buuauthorCangül, Hakan
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.tr_TR
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.tr_TR
dc.contributor.scopusid35772174800tr_TR
dc.contributor.scopusid8911611600tr_TR
dc.date.accessioned2022-09-05T08:13:27Z
dc.date.available2022-09-05T08:13:27Z
dc.date.issued2010-04
dc.description.abstractArthrogryposis, renal dysfunction and cholestasis syndrome (ARC) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells. Mutations in VPS33B account for most cases of ARC. We identified mutations in VIPAR (also called C14ORF133) in individuals with ARC without VPS33B defects. We show that VIPAR forms a functional complex with VPS33B that interacts with RAB11A. Knockdown of vipar in zebrafish resulted in biliary excretion and E-cadherin defects similar to those in individuals with ARC. Vipar-and Vps33b-deficient mouse inner medullary collecting duct (mIMDC-3) cells expressed membrane proteins abnormally and had structural and functional tight junction defects. Abnormal Ceacam5 expression was due to mis-sorting toward lysosomal degradation, but reduced E-cadherin levels were associated with transcriptional downregulation. The VPS33B-VIPAR complex thus has diverse functions in the pathways regulating apical-basolateral polarity in the liver and kidney.en_US
dc.description.sponsorshipChildren Liver Disease Foundationen_US
dc.description.sponsorshipFramework 6 IP EUTRACC (LSGH CT 2006037445)en_US
dc.description.sponsorshipEuropean Molecular Biology Organization (EMBO) (ASTF 121:2007)en_US
dc.description.sponsorshipEuropean Science Foundation (ESF) European Commission (2008)en_US
dc.description.sponsorshipUK Research & Innovation (UKRI) Biotechnology and Biological Sciences Research Council (BBSRC) (BB/H002308/1)en_US
dc.description.sponsorshipARC syndrome associationen_US
dc.description.sponsorshipChildren Living with Inherited Metabolic Diseases (CLIMB)en_US
dc.description.sponsorshipBirmingham Children's Hospital Research Foundation (BCHRF)en_US
dc.description.sponsorshipWellChilden_US
dc.description.sponsorshipWellcome Trust European Commissionen_US
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) (ZIAHD008807)en_US
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) (R01DK035652)en_US
dc.description.sponsorshipNIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) (P30DK034928)en_US
dc.identifier.citationCullinane, A. R. vd. (2010). "Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization". Nature Genetics, 42(4), 303-312.en_US
dc.identifier.endpage312tr_TR
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.issue4tr_TR
dc.identifier.pubmed20190753tr_TR
dc.identifier.scopus2-s2.0-77950300024tr_TR
dc.identifier.startpage303tr_TR
dc.identifier.urihttps://doi.org/10.1038/ng.538
dc.identifier.urihttps://www.nature.com/articles/ng.538
dc.identifier.urihttp://hdl.handle.net/11452/28454
dc.identifier.volume42tr_TR
dc.identifier.wos000276150500009tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherNature Portfolioen_US
dc.relation.collaborationYurt içitr_TR
dc.relation.collaborationYurt dışıtr_TR
dc.relation.collaborationSanayitr_TR
dc.relation.journalNature Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectRecycling endosomesen_US
dc.subjectCarcinoembryonic antigenen_US
dc.subjectIntracellular traffickingen_US
dc.subjectPlasma-membraneen_US
dc.subjectArc syndromeen_US
dc.subjectE-cadherinen_US
dc.subjectMyosin VBen_US
dc.subjectCellen_US
dc.subjectComplexen_US
dc.subjectRab11en_US
dc.subjectGenetics & heredityen_US
dc.subjectDanio rerioen_US
dc.subject.emtreeLymphocyte antigenen_US
dc.subject.emtreeMembrane proteinen_US
dc.subject.emtreeProtein ceacam 5en_US
dc.subject.emtreeProtein viparen_US
dc.subject.emtreeRab11 proteinen_US
dc.subject.emtreeRab11a proteinen_US
dc.subject.emtreeUnclassified drugen_US
dc.subject.emtreeUvomorulinen_US
dc.subject.emtreeAnimal experimenten_US
dc.subject.emtreeAnimal modelen_US
dc.subject.emtreeArthrogryposisen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeBiliary excretionen_US
dc.subject.emtreeCholestasisen_US
dc.subject.emtreeControlled studyen_US
dc.subject.emtreeDown regulationen_US
dc.subject.emtreeGene mutationen_US
dc.subject.emtreeKidney dysfunctionen_US
dc.subject.emtreeMouseen_US
dc.subject.emtreeNonhumanen_US
dc.subject.emtreePhenotypeen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeProtein degradationen_US
dc.subject.emtreeProtein expressionen_US
dc.subject.emtreeProtein functionen_US
dc.subject.emtreeProtein interactionen_US
dc.subject.emtreeProtein structureen_US
dc.subject.emtreeTight junctionen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, genetically modifieden_US
dc.subject.meshArthrogryposisen_US
dc.subject.meshCadherinsen_US
dc.subject.meshCarrier proteinsen_US
dc.subject.meshCell polarityen_US
dc.subject.meshCholestasisen_US
dc.subject.meshEpitheliumen_US
dc.subject.meshHumansen_US
dc.subject.meshKidney diseasesen_US
dc.subject.meshMembrane proteinsen_US
dc.subject.meshMiceen_US
dc.subject.meshMutationen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshSyndromeen_US
dc.subject.meshTight junctionsen_US
dc.subject.meshZebrafishen_US
dc.subject.meshZebrafish proteinsen_US
dc.subject.scopusGray Platelet Syndrome; Megakaryocytes; Blood Plateletsen_US
dc.subject.wosGenetics & heredityen_US
dc.titleMutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarizationen_US
dc.typeArticle
dc.wos.quartileQ1en_US

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