The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes
- Universitat de València, Spain
- Ludwig-Maximilians-Universität München, Germany
- Klinikum der Universtaet Muenchen, Germany
- Eidgenössische Technische Hochschule Zürich, Switzerland
- ETH Zürich, Switzerland
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
Maria Benito-Jardón
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).
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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The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes
eLife 6:e22264.
https://doi.org/10.7554/eLife.22264
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