From: Structure, signal transduction, activation, and inhibition of integrin αIIbβ3
Proteins | Function | Phenotype of knockout mice | reference |
---|---|---|---|
Talin | support integrin activation, link ECM and cytoskeleton | impaired platelet aggregation and adhesion, spontaneous hemorrhage and pathological bleeding | [117] |
Kindlin-3 | support integrin activation, platelet aggregation, platelet adhesion | severe bleeding and resistance to arterial thrombosis | [46] |
Paxillin | support αIIbβ3 activation, influence focal adhesion | delayed spreading, impaired migration | [118] |
Vinculin | regulate mechanical coupling, cell adhesion, control focal adhesion formation | normal fibrinogen binding, aggregation, spreading, actin organization, clot retraction, prolonged bleeding time | [119] |
Rap1 | stimulate integrin activation | impaired spreading on fibrinogen, prolonged tail bleeding time, and reduced platelet aggregation. | [30] |
Filamin | modulate actin crosslinking, cell migration | increased tail bleeding time, macrothrombocytopenia | |
ADAP | support αIIbβ3 activation, stable adhesion, cytoskeletal reorganization | shorter life span, microthrombocytopenia, impaired cytoskeletal reorganization, and thrombus formation | |
ILK | support αIIbβ3 activation | impaired ligand-binding, granule secretion, and platelets aggregation | |
Profilin | regulate actin rearrangement | microthrombocytopenia, accelerated integrin inactivation | [91] |
Cofilin | promote F-actin assembly, thrombus stabilization, actin organization | microthrombocytopenia, unstable adhesion | |
Twf2a | suppress cytoskeletal dynamics | accelerated arterial thrombus formation, faster tail bleeding time, and mild macrothrombocytopenia | [106] |
SHARPIN | inhibit integrin activation | increased binding of fibrinogen to αIIbβ3 and impaired thrombus formation | [104] |
actinin | trigger adhesion maturation | enhance force generation, impaired mechanotransduction | [121] |
RhoA | coordinate changes in the actin cytoskeleton, actin stress fiber formation | defective platelet production and marked thrombocytopenia | [122] |
Cdc42 | facilitate filopodial protrusions and lamellipodia formation, cytoskeletal rearrangements | severe thrombocytopenia, macrothrombocytopenia, abnormal platelet morphology, impaired platelet function | |
Rac1 | |||
Arf6 | regulate endocytic trafficking, actin cytoskeleton remodeling, and lipid metabolism | enhanced spreading on fibrinogen and clot retraction | [115] |