Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility.
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.
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia.
Bipul R
BR
Acharya
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia.
Selwin K
SK
Wu
Mechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, Singapore.
Zi Zhao
ZZ
Lieu
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia; Centre for Microscopy and Microanalysis, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia.
Robert G
RG
Parton
Biotechnology Center, Technical University Dresden, Tatzberg 47/49, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Stephan W
SW
Grill
Mechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, Singapore.
Alexander D
AD
Bershadsky
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia.
Guillermo A
GA
Gomez
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia. Electronic address: a.yap@uq.edu.au.
Alpha S
AS
Yap
D008841:Actin Cytoskeleton / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism; D000080865:Formins; D055785:Gene Knockdown Techniques; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D055550:Protein Stability; D015203:Reproducibility of Results; D013312:Stress, Physiological; D019108:Tight Junctions / Q000378:metabolism; D051178:alpha Catenin
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C108962:DIAPH1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D051178:alpha Catenin; D000205:Actomyosin; D024462:Myosin Type II
actomyosin; epithelial barrier; formins; mDia1; tissue mechanics; αE-catenin