Platelet adhesion: a game of catch and release

The interaction of circulating platelets with the vessel wall involves a process of cell catch and release, regulating cell rolling, skipping, or firm adhesion and leading to thrombus formation in flowing blood. In this regard, the interaction of platelet glycoprotein Ibalpha (GPIbalpha) with its adhesive ligand, vWF, is activated by shear force and critical for platelet adhesion to the vessel wall. In this issue of the JCI, Yago and colleagues show how gain-of-function mutations in the GPIbalpha-binding vWF A1 domain disrupt intramolecular interactions within WT vWF A1 that regulate binding to GPIbalpha and flow-enhanced platelet rolling and adhesion (see the related article beginning on page 3195). Together, these studies reveal molecular mechanisms regulating GPIbalpha-vWF bond formation and platelet adhesion under shear stress.