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

Abstract	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.
Authors	Gabriele Jedlitschky, Marco Cattaneo, Lena E Lubenow, Dieter Rosskopf, Anna Lecchi, Andrea Artoni, Giovanna Motta, Juliane Niessen, Heyo K Kroemer, Andreas Greinacher
Journal	The American journal of pathology (Am J Pathol) Vol. 176 Issue 3 Pg. 1097-103 (Mar 2010) ISSN: 1525-2191 [Electronic] United States
PMID	20133816 (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
Topics	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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