Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage : evidence from patients with delta-storage pool deficiencies

We previously showed that the MRP4 (ABCC4) transporter is expressed in human platelet δ-granules and may be involved in ADP transport. We now demonstrate by immunoblotting and immunofluorescence microscopy that platelet MRP4 is absent in two patients with a platelet δ-storage pool deficiency (δ-SPD)-like phenotype with reduced platelet adenine nucleotide (AN) but normal serotonin levels, whereas their other membrane marker proteins of platelet granules were normally expressed and localized. In these patients, MRP4 was present in lymphocytes, and the coding region of their MRP4/ABCC4 gene did not show any mutation that explained the lack of expression. In platelets with "classic" δ-SPD (low AN and serotonin levels), MRP4 was quantitatively (immunoblot) normal, but, like other δ-granules membrane marker proteins (eg, LAMP2), was mostly displaced from δ-granules to patches at the plasma membrane, suggesting that platelets with classic δ-SPD have an abnormality that impairs the assembly of normal δ-granules. Thus, defective expression of platelet MRP4 is associated with selective defect in AN storage. The genetic basis of the new δ-SPD phenotype remains to be elucidated. Copyright