Dynein Regulates Epithelial Polarity and the Apical Localization of stardust A mRNA 英文参考文献.docVIP

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Dynein Regulates Epithelial Polarity and the Apical Localization of stardust A mRNA 英文参考文献.doc

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Dynein Regulates Epithelial Polarity and the Apical Localization of stardust A mRNA 英文参考文献

DyneinRegulatesEpithelialPolarity andtheApicalLocalizationofstardustAmRNA Sally Horne-Badovinac, David Bilder* DepartmentofMolecularandCellBiology,UniversityofCaliforniaBerkeley,Berkeley,California,UnitedStatesofAmerica Intense investigation has identified an elaborate protein network controlling epithelial polarity. Although precise subcellulartargetingofapicalandbasolateraldeterminantsisrequiredforepithelialarchitecture,littleisknownabout how the individual determinant proteins become localized within the cell. Through a genetic screen for epithelial defectsintheDrosophilafolliclecells,wehavefoundthatthecytoplasmicDyneinmotorisanessentialregulatorof apico–basalpolarity.OurdatasuggestthatDyneinactsthroughthecytoplasmicscaffoldingproteinStardust(Sdt)to localizethetransmembraneproteinCrumbs,inpartthroughtheapicaltargetingofspecific sdtmRNAisoforms.We havemappedthesdtmRNAlocalizationsignaltoanalternativelysplicedcodingexon.Intriguingly,thepresenceor absenceofthisexoncorrespondstoadevelopmentalswitchinsdtmRNAlocalizationinwhichapicaltranscriptsare only found during early stages of epithelial development, while unlocalized transcripts predominate in mature epithelia.ThisworkrepresentsthefirstdemonstrationthatDyneinisrequiredforepithelialpolarityandsuggeststhat mRNAlocalizationmayhaveafunctionalroleintheregulationofapico–basalorganization.Moreover,weintroducea unique mechanism in which alternative splicing of a coding exon is used to control mRNA localization during development. Citation:Horne-BadovinacS,BilderD(2008)DyneinregulatesepithelialpolarityandtheapicallocalizationofstardustAmRNA.PLoSGenet4(1):e8.doi:10.1371/journal.pgen. 0040008 Stardust/MPP5 (Sdt), which binds Crb’s cytoplasmic tail throughits PDZ (PSD-95/Discs large/ZO-1) domain [9–12]. A Introduction A polarized architecture increases the level of sophisti- cationatwhichcellscaninteractwiththeirneighborsandthe environment.Thus,itisnotsurprisingthathighlypolarized epithelia have become the predomina