Calmodulin interacts with the platelet ADP receptor P2Y1

P2Y(1) [P2 (purinergic type-2)-receptor 1] is a G-protein-coupled ADP receptor that regulates platelet activation and ADP-induced Ca2+ signalling. Studies using P2Y(1)-knockout mice, G(q)-deficient mice or P2Y(1)-selective inhibitors have previously identified a key role for P2Y(1) in pathophysiological thrombus formation at high shear stress. We provide evidence that a positively charged juxtamembrane sequence within the cytoplasmic C-terminal tail of P2Y(1) can bind directly to the cytosolic regulatory protein calmodulin. Deletion by mutagenesis of the calmodulin-binding domain of P2Y(1) inhibits intracellular Ca2+ flux in transfected cells. These results suggest that the interaction of calmodulin with the P2Y(1) C-terminal tail may regulate P2Y(1)-dependent platelet aggregation.