Display Settings:

Format

Send to:

Choose Destination
Biol Open. 2012 Nov 15;1(11):1128-40. doi: 10.1242/bio.20122428. Epub 2012 Sep 11.

Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation.

Author information

  • 1Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht , PO Box 85164, 3508 AD Utrecht , The Netherlands.

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 α-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.

KEYWORDS:

Actomyosin; Cell–cell adhesion; E-cadherin; Junction formation; Mechanotransduction; Vinculin

PMID:
23213393
[PubMed]
PMCID:
PMC3507192
Free PMC Article

Images from this publication.See all images (7)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk