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Lowe Syndrome Protein OCRL1 Supports Maturation of Polarized Epithelial Cells 英文参考文献
LoweSyndromeProteinOCRL1SupportsMaturationof
PolarizedEpithelialCells
AdamG.Grieve1.¤,RachelD.Daniels1.,ElenaSanchez-Heras1,MatthewJ.Hayes1,StephenE.Moss1,
KarlMatter1,MartinLowe2,TimothyP.Levine1*
1Department of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom, 2Faculty of Life Sciences, University of Manchester, Manchester, United
Kingdom
Abstract
Mutations in the inositol polyphosphate 5-phosphatase OCRL1 cause Lowe Syndrome, leading to cataracts, mental
retardationandrenalfailure.WenotedthatcelltypesaffectedinLoweSyndromearehighlypolarized,andthereforewe
studiedOCRL1inepithelialcellsastheymaturefromisolatedindividualcellsintopolarizedsheetsandcystswithextensive
communicationbetweenneighbouringcells.WeshowthataproportionofOCRL1targetsintercellularjunctionsattheearly
stagesoftheirformation,co-localizingbothwithadherensjunctionalcomponentsandwithtightjunctionalcomponents.
Correlating with this distribution, OCRL1 forms complexes with junctional components a-catenin and zonula occludens
(ZO)-1/2/3.DepletionofOCRL1inepithelialcellsgrowingasasheetinhibitsmaturation;cellsremainflat,failtopolarize
apicalmarkersandalsoshowreducedproliferation.Theeffectonshapeisrevertedbyre-expressedOCRL1andrequiresthe
59-phosphatase domain, indicating that down-regulation of 5-phosphorylated inositides is necessary for epithelial
development.TheeffectofOCRL1inepithelialmaturationisseenmorestronglyin3-dimensionalcultures,whereepithelial
cellslackingOCRL1notonlyfailtoformacentrallumen,butalsodonothavethecorrectintracellulardistributionofZO-1,
suggestingthatOCRL1functionsearlyinthematurationofintercellularjunctionswhencellsgrowascysts.AroleofOCRL1
injunctionsofpolarizedcellsmayexplainthepatternoforgansaffectedinLoweSyndrome.
Citation:GrieveAG,DanielsRD,Sanchez-HerasE,HayesMJ,MossSE,etal.(2011)LoweSyndromeProteinOCRL1SupportsMaturationofPolarizedEpithelial
Cells.PLoSONE6(8):e24044.doi:10.1371/journal.pone.0024044
Editor:QuanshengDu,GeorgiaHealthSciencesUniversity,Unite
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