Calmodulin interacts with the platelet ADP receptor P2Y1.
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.
Arthur
Jane F
JF
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. jane.arthur@med.monash.edu.au
Shen
Yang
Y
Mu
Fi-Tjen
FT
Leon
Catherine
C
Gachet
Christian
C
Berndt
Michael C
MC
Andrews
Robert K
RK
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
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