Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells

Andrew M. Tilston-Lünel, Kathryn E. Haley, Nicolas F. Schlecht, Yanhua Wang, Abigail L.D. Chatterton, Susana Moleirinho, Ailsa Watson, Harinder S. Hundal, Michael B. Prystowsky, Frank J. Gunn-Moore, Paul A. Reynolds

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Crumbs 3 (CRB3) is a component of epithelial junctions, which has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion, and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, we describe novel data demonstrating that, as with previous studies on CRB3a, CRB3b also promotes the formation of tight junctions (TJs). However, significantly we demonstrate that the 4.1-ezrin-radixin-moesin-binding motif of CRB3b is required for CRB3b functionality and that ezrin binds to the FBM of CRB3b. Furthermore, we show that ezrin contributes to CRB3b functionality and the correct distribution of TJ proteins. We demonstrate that both CRB3 isoforms are required for the production of functionally mature TJs and also the localization of ezrin to the plasma membrane. Finally, we demonstrate that reduced CRB3b expression in head and neck squamous cell carcinoma (HNSCC) correlates with cytoplasmic ezrin, a biomarker for aggressive disease, and shows evidence that while CRB3a expression has no effect, low CRB3b and high cytoplasmic ezrin expression combined may be prognostic for HNSCC.

Original languageEnglish (US)
Pages (from-to)439-455
Number of pages17
JournalJournal of Molecular Cell Biology
Volume8
Issue number5
DOIs
StatePublished - Oct 1 2016

    Fingerprint

Keywords

  • CRB3
  • FBM
  • FERM proteins
  • crumbs
  • ezrin
  • tight junctions

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tilston-Lünel, A. M., Haley, K. E., Schlecht, N. F., Wang, Y., Chatterton, A. L. D., Moleirinho, S., Watson, A., Hundal, H. S., Prystowsky, M. B., Gunn-Moore, F. J., & Reynolds, P. A. (2016). Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells. Journal of Molecular Cell Biology, 8(5), 439-455. https://doi.org/10.1093/jmcb/mjw020