Molecular mechanisms of platelet P2Y(12) 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), P2Y(1) and P2Y(12). 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 P2Y(1) and P2Y(12) receptor regulation, with particular emphasis on the structural motifs within the P2Y(12) receptor, which are required to maintain regulatory protein interaction. The implications of these findings for platelet responsiveness are also discussed.
School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Margaret R
MR
Cunningham
Shaista P
SP
Nisar
Stuart J
SJ
Mundell
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D008969:Molecular Sequence Data; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
C548576:P2RY12 protein, human; D058925:Receptors, Purinergic P2Y12