Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate

Abstract Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance platelet polyphosphate in blood coagulation; however, mechanistic details homeostasis mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated platelets was implicated thrombosis vivo. We used bioinformatic analyses omics data to identify XPR1 as major phosphate transporter platelets. messenger RNA protein expression inversely correlated with intracellular content release. Pharmacological interference activity increased stores, led enhanced platelet-driven coagulation, amplified thrombus formation under flow via polyphosphate/factor XII pathway. Conditional gene deletion Xpr1 resulted accumulation, accelerated arterial thrombosis, augmented activated pulmonary embolism without increasing bleeding mice. These an integral regulator metabolism reveal fundamental role for thrombosis.