Platelet Immunoreceptor Tyrosine-Based Activation Motif (ITAM) Signaling and Vascular Integrity

Platelets are well-known for their critical role in hemostasis, i.e. the prevention of blood loss at sites of mechanical vessel injury. Inappropriate platelet activation and adhesion, however, can lead to thrombotic complications, such as myocardial infarction and stroke. To fulfill its role in hemostasis, the platelet is equipped with various G protein-coupled receptors (GPCRs) that mediate the response to soluble agonists such as thrombin, ADP, and thromboxane A2. In addition to GPCRs, platelets express three glycoproteins (GP) that belong to the family of immunoreceptor tyrosine-based activation motif (ITAM) receptors: Fc receptor (FcR) γ chain, which is non-covalently associated with the GPVI collagen receptor, C-type lectin 2 (CLEC2), the receptor for podoplanin, and FcγRIIA, a low-affinity receptor for immune complexes. While both genetic and chemical approaches have documented a critical role for platelet GPCRs in hemostasis, the contribution of ITAM receptors to this process is less defined. Studies performed over the last decade, however, have identified new roles for platelet ITAM signaling in vascular integrity in utero and at sites of inflammation. The purpose of this review is to summarize recent findings on how platelet ITAM signaling controls vascular integrity, both in the presence and absence of mechanical injury