Platelet Integrins: Critical Mediators of Haemostasis and Pathological Thrombus Formation

Abstract

Platelets are small anucleated blood cells that survey the integrity of the blood vasculature, ready to rapidly seal injuries in order to limit blood loss. Integrins on the platelet surface are essential mediators of this haemostatic function: their ability to rapidly shift from a low- to a high-affinity conformation to bind their ligands allows the platelet to quickly adapt an adhesive state, facilitating stable adhesion to the extracellular matrix and platelet aggregation under highly dynamic blood flow conditions. Furthermore, integrins act as bidirectional signalling machines that regulate cytoskeletal rearrangements and cellular effector functions. While integrin function is critical for haemostasis, it is also a prerequisite for pathological thrombus formation, resulting in vessel occlusion, ischaemia, and infarction of vital organs. Over the last decades, many investigators have provided fundamental insights into the cellular and molecular basis of platelet integrin function and regulation, particularly of the major integrin, αIIbβ3, advancing not only our understanding of platelet function but also of integrins in general. In this chapter, we will give an overview on the role of platelet integrins in normal platelet physiology and disease. We will further describe the inside-out signalling pathways that control integrin activity—with a special focus on talin and kindlin-3—as well as the outside-in signalling pathways initiated by the ligand-occupied integrins themselves.