Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation

Floor Twiss, Quint Le Duc, Suzanne Van Der Horst, Hamid Tabdili, Gerard Van Der Krogt, Ning Wang, Holger Rehmann, Stephan Huveneers, Deborah E. Leckband, Johan De Rooij

Research output: Contribution to journalArticle

Abstract

Proper regulation of the formation and stabilization of epithelial cell-cell adhesion is crucial in embryonic morphogenesis and tissue repair processes. Defects in this process lead to organ malformation and defective epithelial barrier function. A combination of chemical and mechanical cues is used by cells to drive this process. We have investigated the role of the actomyosin cytoskeleton and its connection to cell-cell junction complexes in the formation of an epithelial barrier in MDCK cells. We find that the E-cadherin complex is sufficient to mediate a functional link between cell-cell contacts and the actomyosin cytoskeleton. This link involves the actin binding capacity of a-catenin and the recruitment of the mechanosensitive protein Vinculin to tensile, punctate cell- cell junctions that connect to radial F-actin bundles, which we name Focal Adherens Junctions (FAJ). When cell-cell adhesions mature, these FAJs disappear and linear junctions are formed that do not contain Vinculin. The rapid phase of barrier establishment (as measured by Trans Epithelial Electrical Resistance (TER)) correlates with the presence of FAJs. Moreover, the rate of barrier establishment is delayed when actomyosin contraction is blocked or when Vinculin recruitment to the Cadherin complex is prevented. Enhanced presence of Vinculin increases the rate of barrier formation. We conclude that E-cadherin-based FAJs connect forming cell-cell adhesions to the contractile actomyosin cytoskeleton. These specialized junctions are sites of Cadherin mechanosensing, which, through the recruitment of Vinculin, is a driving force in epithelial barrier formation.

Original languageEnglish (US)
Pages (from-to)1128-1140
Number of pages13
JournalBiology Open
Volume1
Issue number11
DOIs
StatePublished - Nov 15 2012

Keywords

  • Actomyosin
  • Cell-cell adhesion
  • E-cadherin
  • Junction formation
  • Mechanotransduction
  • Vinculin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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  • Cite this

    Twiss, F., Le Duc, Q., Van Der Horst, S., Tabdili, H., Van Der Krogt, G., Wang, N., Rehmann, H., Huveneers, S., Leckband, D. E., & De Rooij, J. (2012). Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation. Biology Open, 1(11), 1128-1140. https://doi.org/10.1242/bio.20122428