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Table 1 Proteins associated with the connection of ECM to the cytoskeleton

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

[88, 120]

ADAP

support αIIbβ3 activation, stable adhesion, cytoskeletal reorganization

shorter life span, microthrombocytopenia, impaired cytoskeletal reorganization, and thrombus formation

[93] [92]

ILK

support αIIbβ3 activation

impaired ligand-binding, granule secretion, and platelets aggregation

[79, 80]

Profilin

regulate actin rearrangement

microthrombocytopenia, accelerated integrin inactivation

[91]

Cofilin

promote F-actin assembly, thrombus stabilization, actin organization

microthrombocytopenia, unstable adhesion

[93, 94]

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

[123, 124]

Rac1

Arf6

regulate endocytic trafficking, actin cytoskeleton remodeling, and lipid metabolism

enhanced spreading on fibrinogen and clot retraction

[115]