A mechanosensitive RhoA pathway that protects epithelia against acute tensile stress.

Bipul R Archarya, Alexander Nestor-Bergmann, Xuan Liang, Shafali Gupta, Kinga Duszyc, Estelle Gauquelin, Guillermo A Gomez, Srikanth Budnar, Philippe Marcq, Oliver Jensen, Zev Bryant, Alpha S Yap

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Adherens junctions are tensile structures that couple epithelial cells together.
    Junctional tension can arise from cell-intrinsic application of contractility or from the cell-extrinsic forces of tissue movement. Here we report a mechanosensitive
    signalling pathway that activates RhoA at adherens junctions to preserve epithelial integrity in response to acute tensile stress. We identify Myosin VI as the forcesensor, whose association with E-cadherin is enhanced when junctional tension is increased by mechanical monolayer stress. Myosin VI promotes recruitment of the heterotrimeric protein Gα12 to E-cadherin, where it signals for p114 RhoGEF to activate RhoA. Despite its potential to stimulate junctional actomyosin and further increase contractility, tension-activated RhoA signalling was necessary to preserve epithelial integrity. This is explained by an increase in tensile strength, especially at the multicellular vertices of junctions, that is due to mDia1-mediated actin assembly.
    Original languageEnglish
    Pages (from-to)439-452
    JournalDevelopmental cell
    Volume47
    Early online date11 Oct 2018
    DOIs
    Publication statusPublished - 19 Nov 2018

    Keywords

    • Epithelia
    • mechanotransduction
    • tension
    • RhoA
    • Myosin VI

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