Model of the regulation of αIIbβ3 activation. (A) In resting platelets, FLNa is constitutively associated with αIIbβ3 (β3 CT) through its Ig repeat 21. After platelet activation, FLNa interacts with an unknown FLNa partner through Ig repeat 21, leading to FLNa release from βCT. In this model, FLNa-free βCT binding sites would now allow recruitment of talin and kindlin to βCT required for αIIbβ3 activation. (B) In resting platelets, FLNa is constitutively associated with αIIbβ3 (β3 CT) through its Ig repeat 21. The dissociation of FLNa from β3 could be the result of a conformational change in FLNa that occurred during platelet activation and in the presence of shear, leading to a decreased affinity and dissociation of FLNa from β3.