CPEB-mediated Zo-1 mRnA localization isrequired for epithelial tight-junction assemblyand cell polarity

摘要

CPEB is a translational regulatory sequence-specific RnA-binding protein that controls germcell development. Here we show that CPEB heterozygous female mice are fertile but containdisorganized mammary epithelial cells, in which zonal occludens-1 and claudin-3, apical tightjunction proteins, are mislocalized. CPEB depletion from mammary epithelial cells disrupts zonaloccludens-1 apical localization and tight-junction distribution; conversely, ectopic expressionof CPEB enhances zonal occludens-1 localization. CPEB and zonal occludens-1 mRnA areco-localized apically and zonal occludens-1 3′ untranslated region-binding sites for CPEB arenecessary for RnA localization. In a three-dimensional culture system that models lumencontaining mammary ducts, depletion of CPEB or zonal occludens-1 impairs central cavityformation, indicating a loss of cell polarity. Cavity formation in zonal occludens-1-depleted cellsis rescued when they are transduced with zonal occludens-1 mRnA containing, but not lacking,CPEB-binding sites. our data demonstrate that CPEB-mediated zonal occludens-1 mRnAlocalization is essential for tight-junction assembly and mammary epithelial cell polarity.