Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Bipul R. Acharya, Selwin K. Wu, Zi Zhao Lieu, Robert G. Parton, Stephan W. Grill, Alexander D. Bershadsky, Guillermo A. Gomez, Alpha S. Yap
Formins are a diverse class of actin regulators that influence filament dynamics and organization. Several formins have been identified at epithelial adherens junctions, but their functional impact remains incompletely understood. Here, we tested the hypothesis that formins might affect epithelial interactions through junctional contractility. We focused on mDia1, which was recruited to the zonula adherens (ZA) of established Caco-2 monolayers in response to E-cadherin and RhoA. mDia1 was necessary for contractility at the ZA, measured by assays that include a FRET-based sensor that reports molecular-level tension across αE-catenin. This reflected a role in reorganizing F-actin networks to form stable bundles that resisted myosin-induced stress. Finally, we found that the impact of mDia1 ramified beyond adherens junctions to stabilize tight junctions and maintain the epithelial permeability barrier. Therefore, control of tissue barrier function constitutes a pathway for cadherin-based contractility to contribute to the physiology of established epithelia.

Graphical abstract

Teaser

Adherens junctions are contractile structures. Acharya et al. find that the formin mDia1 regulates F-actin organization for effective contractility. mDia1-dependent junctional tension also stabilized components of the tight junction to regulate transepithelial permeability, suggesting that junctional contractility is an element that supports the essential barrier function of post-morphogenetic epithelia.


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