Proteolytic processing of platelet receptors

ESSENTIALS: Metalloproteinases regulate release/shedding of bioactive membrane proteins. Shedding is critically important for normal cell function in the vasculature. Levels of platelet receptors GPIb‐IX‐V and GPVI are regulated by metalloproteolytic shedding. The premier platelet sheddases belong to the A Disintegrins And Metalloproteinase (ADAMs) family. Modulating ADAM activity may alter platelet adheso‐signalling receptor density and function. Platelets have a major role in hemostasis and an emerging role in biological processes including inflammation and immunity. Many of these processes require platelet adhesion and localization at sites of tissue damage or infection and regulated platelet activation, mediated by platelet adheso‐signalling receptors, glycoprotein (GP) Ib‐IX‐V and GPVI. Work from a number of laboratories has demonstrated that levels of these receptors are closely regulated by metalloproteinases of the A Disintegrin And Metalloproteinase (ADAM) family, primarily ADAM17 and ADAM10. It is becoming increasingly evident that platelets have important roles in innate immunity, inflammation, and in combating infection that extends beyond processes of hemostasis. This overview will examine the molecular events that regulate levels of platelet receptors and then assess ramifications for these events in settings where hemostasis, inflammation, and infection processes are triggered.