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 i...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471730298X |
| _version_ | 1811283495724515328 |
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| author | Bipul R. Acharya Selwin K. Wu Zi Zhao Lieu Robert G. Parton Stephan W. Grill Alexander D. Bershadsky Guillermo A. Gomez Alpha S. Yap |
| author_facet | Bipul R. Acharya Selwin K. Wu Zi Zhao Lieu Robert G. Parton Stephan W. Grill Alexander D. Bershadsky Guillermo A. Gomez Alpha S. Yap |
| author_sort | Bipul R. Acharya |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T02:12:48Z |
| format | Article |
| id | doaj.art-78266f0bc89a48699a31cb4997d97b48 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T02:12:48Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-78266f0bc89a48699a31cb4997d97b482022-12-22T03:07:14ZengElsevierCell Reports2211-12472017-03-0118122854286710.1016/j.celrep.2017.02.078Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional ContractilityBipul R. Acharya0Selwin K. Wu1Zi Zhao Lieu2Robert G. Parton3Stephan W. Grill4Alexander D. Bershadsky5Guillermo A. Gomez6Alpha S. Yap7Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, AustraliaDivision of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, AustraliaMechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, SingaporeDivision of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, AustraliaBiotechnology Center, Technical University Dresden, Tatzberg 47/49, 01307 Dresden, GermanyMechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, SingaporeDivision of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, AustraliaDivision of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, AustraliaFormins 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.http://www.sciencedirect.com/science/article/pii/S221112471730298Xepithelial barrierforminsmDia1actomyosinαE-catenintissue mechanics |
| spellingShingle | Bipul R. Acharya Selwin K. Wu Zi Zhao Lieu Robert G. Parton Stephan W. Grill Alexander D. Bershadsky Guillermo A. Gomez Alpha S. Yap Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility Cell Reports epithelial barrier formins mDia1 actomyosin αE-catenin tissue mechanics |
| title | Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility |
| title_full | Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility |
| title_fullStr | Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility |
| title_full_unstemmed | Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility |
| title_short | Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility |
| title_sort | mammalian diaphanous 1 mediates a pathway for e cadherin to stabilize epithelial barriers through junctional contractility |
| topic | epithelial barrier formins mDia1 actomyosin αE-catenin tissue mechanics |
| url | http://www.sciencedirect.com/science/article/pii/S221112471730298X |
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