Molecular mechanisms of platelet P2Y₁₂ receptor regulation

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.