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 delta-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 delta-storage pool deficiency (delta-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" delta-SPD (low AN and serotonin levels), MRP4 was quantitatively (immunoblot) normal, but, like other delta-granules membrane marker proteins (eg, LAMP2), was mostly displaced from delta-granules to patches at the plasma membrane, suggesting that platelets with classic delta-SPD have an abnormality that impairs the assembly of normal delta-granules. Thus, defective expression of platelet MRP4 is associated with selective defect in AN storage. The genetic basis of the new delta-SPD phenotype remains to be elucidated.
AuthorsGabriele Jedlitschky, Marco Cattaneo, Lena E Lubenow, Dieter Rosskopf, Anna Lecchi, Andrea Artoni, Giovanna Motta, Juliane Niessen, Heyo K Kroemer, Andreas Greinacher
JournalThe American journal of pathology (Am J Pathol) Vol. 176 Issue 3 Pg. 1097-103 (Mar 2010) ISSN: 1525-2191 [Electronic] United States
PMID20133816 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ABCC4 protein, human
  • Adenine Nucleotides
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Adenine Nucleotides (metabolism)
  • Adolescent
  • Adult
  • Blood Platelets (metabolism)
  • Female
  • Gene Expression Regulation
  • Humans
  • Leukocytes (metabolism)
  • Male
  • Multidrug Resistance-Associated Proteins (genetics, metabolism)
  • Phenotype
  • Platelet Function Tests
  • Platelet Storage Pool Deficiency (genetics, metabolism, pathology, physiopathology)
  • Protein Transport
  • RNA, Messenger (genetics, metabolism)
  • Young Adult

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