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

RGD motif Crosstalk
DOI: 10.7554/elife.22264 Publication Date: 2017-01-16T13:03:03Z
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 αIIb is the synergy site located in close proximity RGD motif. We report that mice with dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet bleeding defects due delayed thrombus formation after vessel injury. Additional loss β3 dramatically aggravates bleedings severely compromises smooth muscle coverage vasculature leading embryonic lethality. Cell-based studies revealed dispensable initial contact α5β1 RGD, but essential re-enforce α5β1/αIIbβ3 FN. Our findings demonstrate critical role FN when external forces exceed certain threshold or αvβ3 integrin levels decrease below level.
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