Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility
Bipul R. Acharya,
Selwin K. Wu,
Zi Zhao Lieu,
Robert G. Parton,
Stephan W. Grill,
Alexander D. Bershadsky,
Guillermo A. Gomez,
Alpha S. Yap
Affiliations
Bipul R. Acharya
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia
Selwin K. Wu
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia
Zi Zhao Lieu
Mechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, Singapore
Robert G. Parton
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia
Stephan W. Grill
Biotechnology Center, Technical University Dresden, Tatzberg 47/49, 01307 Dresden, Germany
Alexander D. Bershadsky
Mechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, Singapore
Guillermo A. Gomez
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia
Alpha S. Yap
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia
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.
