| First Author | Benito-Jardón M | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28092265 | Mgi Jnum | J:240616 |
| Mgi Id | MGI:5888803 | Doi | 10.7554/eLife.22264 |
| Citation | Benito-Jardon M, et al. (2017) The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes. Elife 6:e22264 |
| abstractText | Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of alpha5beta1, alphaIIbbeta3 and alphav-class integrins to an RGD-motif. An additional linkage for alpha5 and alphaIIb 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 beta3 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 alpha5beta1 with the RGD, but essential to re-enforce the binding of alpha5beta1/alphaIIbbeta3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when alphavbeta3 integrin levels decrease below a critical level. |
