Molecular mechanisms of platelet P2Y12 receptor regulation

Abstract

Platelets are critical for haemostasis, however inappropriate activation can lead to the development of arterial thrombosis, which can result in heart attack and stroke. ADP is a key platelet agonist that exerts its actions via stimulation of two surface GPCRs (G-protein-coupled receptors), P2Y1 and P2Y12. Similar to most GPCRs, P2Y receptor activity is tightly regulated by a number of complex mechanisms including receptor desensitization, internalization and recycling. In the present article, we review the molecular mechanisms that underlie P2Y1 and P2Y12 receptor regulation, with particular emphasis on the structural motifs within the P2Y12 receptor, which are required to maintain regulatory protein interaction. The implications of these findings for platelet responsiveness are also discussed.