1. Cell Biology
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The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes

  1. Maria Benito-Jardón
  2. Sarah Klapproth
  3. Irene Gimeno-LLuch
  4. Tobias Petzold
  5. Mitasha Bharadwaj
  6. Daniel J Müller
  7. Gabriele Zuchtriegel
  8. Christoph A Reichel
  9. Mercedes Costell  Is a corresponding author
  1. Universitat de València, Spain
  2. Ludwig-Maximilians-Universität München, Germany
  3. Klinikum der Universtaet Muenchen, Germany
  4. Eidgenössische Technische Hochschule Zürich, Switzerland
  5. ETH Zürich, Switzerland
Research Article
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Cite this article as: eLife 2017;6:e22264 doi: 10.7554/eLife.22264

Abstract

Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (FNsyn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of α5β1 with the RGD, but essential to re-enforce the binding of α5β1/αIIbβ3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when αvβ3 integrin levels decrease below a critical level.

Article and author information

Author details

  1. Maria Benito-Jardón

    Biochemistry and Molecular Biology, Universitat de València, Burjassot, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9562-5430
  2. Sarah Klapproth

    Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Irene Gimeno-LLuch

    Biochemistry and Molecular Biology, Universitat de València, Burjassot, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Tobias Petzold

    Medizinische Klinik und Poliklinik, Klinikum der Universtaet Muenchen, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Mitasha Bharadwaj

    Department Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel J Müller

    Department of Biosystems Science and Engineering, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Gabriele Zuchtriegel

    Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Christoph A Reichel

    Departement of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-Universität München, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Mercedes Costell

    Biochemistry and Molecular Biology, Universitat de València, Burjassot, Spain
    For correspondence
    mercedes.costell@uv.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6146-996X

Funding

Ministerio de Economía y Competitividad (National grant)

  • Maria Benito-Jardón
  • Irene Gimeno-LLuch
  • Mercedes Costell

Conselleria Valenciana d'Educació i Ciència (Graduate student fellowship)

  • Maria Benito-Jardón

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Mice were housed in special pathogen free animal facilities. All mouse work was performed in accordance with the Government of the Valencian Community (Spain) guidelines (permission reference A1327395471346). Mice containing the integrin β3 deletion were bred under the permission reference 55.2-1-54-2532-96-2015 (Government of Upper Bavaria). The tail-bleeding and cremaster muscle venules injury assays performed under the permission reference 55.2-1-54-2532-115-12 (Government of Upper Bavaria).

Reviewing Editor

  1. Reinhard Fässler, Max Planck Institute of Biochemistry, Germany

Publication history

  1. Received: October 11, 2016
  2. Accepted: January 15, 2017
  3. Accepted Manuscript published: January 16, 2017 (version 1)
  4. Version of Record published: January 30, 2017 (version 2)
  5. Version of Record updated: March 20, 2018 (version 3)

Copyright

© 2017, Benito-Jardón et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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