Down-regulation and redistribution of GPV/GPVf2, a subunit of von Willebrand factor receptor (GPIb/IX/V complex), on the surface membrane of thrombin-stimulated human platelets.

We have studied down-regulation and redistribution of glycoprotein V (GPV) and its fragment GPVf2, a subunit of a receptor for von Willebrand factor (VWF), on the surface membrane of thrombin and thrombin receptor activating peptide (TRAP) stimulated platelets by using a newly developed GPVf2-specific monoclonal antibody (1D9). Immunoelectron-microscopical studies revealed that about 50% each of total GPV and GPIX were expressed on the surface membrane of the resting human platelets, and about 83% of GPlbalpha was expressed on the surface. In thrombin-stimulated platelets, the surface GPIbalpha, GPIX and GPV, after hydrolysis by thrombin, was converted to GPVf2, translocated from the surface to the intraplatelet pool and then again redistributed to the surface. In TRAP-stimulated platelets, GPIbalpha, GPIX and GPV, without conversion to GPVf2, were translocated from the surface to the intraplatelet pool and then returned to the surface. Ristocetin-induced agglutinations of both the thrombin- and TRAP-stimulated platelets were lowered during the decreased surface expressions of GPIbalpha, GPIX and GPV/GPVf2 and then normalized when these GPs were again redistributed onto the surface, indicating that the redistributed GPIb/IX/Vf2 complex on the surface can act as a VWF receptor as efficiently as an intact GPIb/IX/V.