A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function

Summary

The integrin α_IIbβ₃ on resting platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. α_IIbβ₃ is known to interact with the general integrin-recognition motif RGD (arginine–glycine–aspartate) as well as the fibrinogen-specific γ-chain dodecapeptide; however, it is not known how fibrinogen binding triggers platelet activation. NGR (asparagine–glycine–arginine) is another integrin-recognition sequence present in fibrinogen and this study aims to determine if it plays a role in the interaction between fibrinogen and α_IIbβ₃. NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC₅₀ of 175 μM but failed to inhibit the adhesion of activated platelets to fibrinogen (IC₅₀ > 500 μM). Resting platelet adhesion to mutant fibrinogens lacking the NGR sequences was reduced compared to normal fibrinogen under both static and shear conditions (200 s^-1). However, pre-activated platelets were able to fully spread on all types of fibrinogen. Thus, the NGR motif in fibrinogen is the site that is primarily responsible for the interaction with resting α_IIbβ₃ and is responsible for triggering platelet activation.

Keywords

Platelets - GPIIb-IIIa - fibrinogen - platelet activation

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