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

Gabriele Jedlitschky, Marco Cattaneo, Lena E. Lubenow, Dieter Rosskopf, Anna Lecchi, Andrea Artoni, Giovanna Motta, Juliane Nießen, Heyo K. Kroemer, Andreas Greinacher

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1097-1103
Number of pages7
JournalAmerican Journal of Pathology
Volume176
Issue number3
DOIs
Publication statusPublished - Mar 2010

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Jedlitschky, G., Cattaneo, M., Lubenow, L. E., Rosskopf, D., Lecchi, A., Artoni, A., Motta, G., Nießen, J., Kroemer, H. K., & Greinacher, A. (2010). Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: Evidence from patients with delta-storage pool deficiencies. American Journal of Pathology, 176(3), 1097-1103. https://doi.org/10.2353/ajpath.2010.090425