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

Kentaro Nagaoka, Tsuyoshi Udagawa, Joel D. Richter

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


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.

Original languageEnglish
Article number675
JournalNature communications
Publication statusPublished - 2012
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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