The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes
Müller, Daniel J.
Reichel, Christoph A.
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
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 (Fn1syn/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 Show more
Journal / serieseLife
PublishereLife Sciences Publications
Organisational unit02060 - Departement Biosysteme / Department of Biosystems Science and Engineering
03870 - Müller, Daniel J.
NotesWe acknowledge support from the Spanish Ministry for Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER): Mat2012-38359 (MINECO) and Mat2015-69315 (MINECO/FEDER) as well as from the Sonderforschungsbereich 914 (SFB 914; project B3) granted by the Deutsche Forschungsgemeinschaft (DFG). MB-J was supported by a contract from the Conselleria Valenciana d’Educació i Ciència. We thank Kairbaan Hodivala-Dilke for providing the Itgb3-/- mouse strain and Herbert Schiller for cell lines.
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