Clathrin-mediated integrin αIIbβ3 trafficking controls platelet spreading

AbstractDynamic endocytic and exocytic trafficking of integrins is an important mechanism for cell migration, invasion, and cytokinesis. Endocytosis of integrin can be classified as clathrin dependent and clathrin independent manners. And rapid delivery of endocytic integrins back to the plasma membrane is key intracellular signals and is indispensable for cell movement. Integrin αIIbβ3 plays a critical role in thrombosis and hemostasis. Although previous studies have demonstrated that internalization of fibrinogen-bound αIIbβ3 may regulate platelet activation, the roles of endocytic and exocytic trafficking of integrin αIIbβ3 in platelet activation are unclear. In this study, we found that a selective inhibitor of clathrin-mediated endocytosis pitstop 2 inhibited human platelet spreading on immobilized fibrinogen (Fg). Mechanism studies revealed that pitstop 2 did not block the endocytosis of αIIbβ3 and Fg uptake, but inhibit the recycling of αIIbβ3 to plasma membrane during platelet or CHO cells bearing...