title: Calmodulin interacts with the platelet ADP receptor P2Y1.
abstract: P2Y1 [P2 (purinergic type-2)-receptor 1] is a G-protein-coupled ADP receptor that regulates platelet activation and ADP-induced Ca2+ signalling. Studies using P2Y1-knockout mice, G(q)-deficient mice or P2Y1-selective inhibitors have previously identified a key role for P2Y1 in pathophysiological thrombus formation at high shear stress. We provide evidence that a positively charged juxtamembrane sequence within the cytoplasmic C-terminal tail of P2Y1 can bind directly to the cytosolic regulatory protein calmodulin. Deletion by mutagenesis of the calmodulin-binding domain of P2Y1 inhibits intracellular Ca2+ flux in transfected cells. These results suggest that the interaction of calmodulin with the P2Y1 C-terminal tail may regulate P2Y1-dependent platelet aggregation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. jane.arthur@med.monash.edu.au
authors.forename: Jane F
authors.initials: JF
authors.lastname: Arthur
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Fi-Tjen
authors.initials: FT
authors.lastname: Mu
authors.forename: Catherine
authors.initials: C
authors.lastname: Leon
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Michael C
authors.initials: MC
authors.lastname: Berndt
authors.forename: Robert K
authors.initials: RK
authors.lastname: Andrews
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000502:physiology; D011485:Protein Binding; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002147:Calmodulin; C546382:P2RY1 protein, human; C546383:P2ry1 protein, mouse; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013449:Sulfonamides; D000244:Adenosine Diphosphate; C017967:W 7; D002118:Calcium