Calmodulin interacts with the platelet ADP receptor P2Y₁ Available to Purchase

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.