The leucine-rich repeat region of GP Ibα is important in the interaction of the platelet GP Ib-IX-V complex with immobilized von Willebrand factor under fluid shear stress

Platelets play key roles in physiology, such as the arrest of bleeding following vascular injury, and in pathology, such as mural arterial thrombosis. The initial step in both processes is platelet adhesion to von Willebrand factor (vWf). The adhesion molecule on the platelet surface responsible for this interaction is the platelet glycoprotein (GP) Ib-IX-V complex. This complex consists of four subunits: GP Ibα, GP Ibβ, GP IX, and GP V[1]. The GP Ibα subunit contains the vWf binding site and seven structural motifs of a leucine-rich sequence. The purpose of this study was to investigate the importance of the leucine-rich repeat region of GP Ibα in the interaction of the GP Ib-IX-V complex with immobilized vWf under fluid shear stress. Cells expressing GP Ibα with various point mutations in its leucine-rich repeat region either failed to interact with immobilized vWf or rolled on the surface at higher velocities compared to cells expressing wild-type GP Ibα. These results illustrate the importance of the leucine-rich repeat region of GP Ibα in the receptor-ligand interaction under fluid shear stress