Cortical F-actin stabilization generates apical–lateral patterns of junctional contractility that integrate cells into epithelia
Abstract
E-cadherin cell-cell junctions couple the contractile cortices of epithelial cells together, generating tension within junctions that influences tissue organization. Although junctional tension is commonly studied at the apical zonula adherens, we now report that E-cadherin adhesions induce the contractile actomyosin cortex throughout the apical-lateral axis of junctions. However, cells establish distinct regions of contractile activity even within individual contacts, producing high tension at the zonula adherens but substantially lower tension elsewhere. We demonstrate that N-WASP (also known as WASL) enhances apical junctional tension by stabilizing local F-actin networks, which otherwise undergo stress-induced turnover. Further, we find that cells are extruded from monolayers when this pattern of intra-junctional contractility is disturbed, either when N-WASP redistributes into lateral junctions in H-Ras(V12)-expressing cells or on mosaic redistribution of active N-WASP itself. We propose that local control of actin filament stability regulates the landscape of intra-junctional contractility to determine whether or not cells integrate into epithelial populations.
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SG2 junctions show structural resemblance to tensile lateral networks in cultured simple epithelia but function more like the ZA in providing a continuous tensile network that mechanically couples contractile forces across epidermal sheets to promote barrier-forming TJs.
“Although SG2 junctions show structural resemblance to the tensile lateral networks recently described in cultured simple epithelia36, they function more like the ZA in providing a continuous tensile network that mechanically couples contractile forces across epidermal sheets to promote barrier-forming TJs.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [36]
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Self-citation
- Authors
- Wu, S. K., Gomez, G. A., Michael, M., Verma, S., Cox, H. L., Lefevre, J. G., Parton, R. G., Hamilton, N. A., Neufeld, Z., & Yap, A. S.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Gomez, Guillermo A.
- Yap, Alpha S.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2014-01-12
- Volume
- 16
- Issue
- 2
- Pages
- 167-178
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2021246320
- Cited by
- 230
- References
- 0
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 11 · 2023: 10 · 2022: 14 · 2021: 21 · 2020: 18 · 2019: 18 · 2018: 9 · 2017: 30 · 2016: 31 · 2015: 32 · 2014: 17
- FWCI
- 18.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- E-cadherin, cell-cell contact, actomyosin cortex, F-actin stabilization, N-WASP, WASL, junctional tension, adherens junctions, cell extrusion, H-Ras V12, actin turnover
- MeSH terms
- Actins, Humans, Intercellular Junctions, Cadherins, Caco-2 Cells, Wiskott-Aldrich Syndrome Protein, Neuronal
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