Platelet ITAM signaling

G protein-coupled receptors (GPCRs) like PAR1/4 and P2Y12 have long been known for their critical role in hemostasis. In contrast, deficiency in the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors glycoprotein (GP)VI or C-type lectin-like receptor (CLEC)-2 is associated with only a mild bleeding diathesis in humans and mice. This review summarizes recent developments on the physiological importance of platelet ITAM signaling as well as the molecular mechanisms facilitating this signaling pathway.

Genetic experiments identified a critical role for platelet CLEC-2 signaling in the formation of lymphatic vessels during development. Similarly, signaling by both GPVI and CLEC-2, but not GPCRs, is required for the maintenance of vascular integrity at sites of inflammation in the adult. The molecular mechanisms underlying ITAM signaling in platelets continue to be refined.

Platelet ITAM signaling plays a key role for the maintenance of vascular integrity in development and the adult. This novel form of hemostasis differs from hemostasis at sites of vascular injury in that it does not depend on major platelet adhesion receptors or GPCR signaling.