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Defining functional interactions during biogenesis of epithelial junctions

Author

Listed:
  • J. C. Erasmus

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London)

  • S. Bruche

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London
    Present address: Department of Physiology, Anatomy and Genetics, University of Oxford)

  • L. Pizarro

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London
    Imperial College London)

  • N. Maimari

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London
    Faculty of Engineering, Imperial College London)

  • T. Poggioli

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London
    Present address: The Brigham Regenerative Medicine Center, Harvard Medical School)

  • C. Tomlinson

    (Faculty of Medicine, Imperial College London)

  • J. Lees

    (University College London)

  • I. Zalivina

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London
    Present address: King's College London)

  • A. Wheeler

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London
    Present address: University of Edinburgh Western General Hospital)

  • A. Alberts

    (Van Andel Institute)

  • A. Russo

    (Imperial College London)

  • V. M. M. Braga

    (National Heart and Lung Institute, Faculty of Medicine, Imperial College London)

Abstract

In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases.

Suggested Citation

  • J. C. Erasmus & S. Bruche & L. Pizarro & N. Maimari & T. Poggioli & C. Tomlinson & J. Lees & I. Zalivina & A. Wheeler & A. Alberts & A. Russo & V. M. M. Braga, 2016. "Defining functional interactions during biogenesis of epithelial junctions," Nature Communications, Nature, vol. 7(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13542
    DOI: 10.1038/ncomms13542
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