CPEB-mediated ZO-1 mRNA localization is required for epithelial tight-junction assembly and cell polarity

Kentaro Nagaoka, Tsuyoshi Udagawa and Joel D. Richter ()
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Kentaro Nagaoka: Program in Molecular Medicine, University of Massachusetts Medical School
Tsuyoshi Udagawa: Program in Molecular Medicine, University of Massachusetts Medical School
Joel D. Richter: Program in Molecular Medicine, University of Massachusetts Medical School

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: Abstract CPEB is a translational regulatory sequence-specific RNA-binding protein that controls germ cell development. Here we show that CPEB heterozygous female mice are fertile but contain disorganized mammary epithelial cells, in which zonal occludens-1 and claudin-3, apical tight-junction proteins, are mislocalized. CPEB depletion from mammary epithelial cells disrupts zonal occludens-1 apical localization and tight-junction distribution; conversely, ectopic expression of CPEB enhances zonal occludens-1 localization. CPEB and zonal occludens-1 mRNA are co-localized apically and zonal occludens-1 3′ untranslated region-binding sites for CPEB are necessary for RNA localization. In a three-dimensional culture system that models lumen-containing mammary ducts, depletion of CPEB or zonal occludens-1 impairs central cavity formation, indicating a loss of cell polarity. Cavity formation in zonal occludens-1-depleted cells is 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 mRNA localization is essential for tight-junction assembly and mammary epithelial cell polarity.

Date: 2012
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DOI: 10.1038/ncomms1678

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