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

The American Journal of Pathology
G JedlitschkyAndreas Greinacher

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.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J D EricksonB J Hoffman
Jul 20, 2002·Current Molecular Medicine·M Huizing, W A Gahl
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·M Cattaneo
Jul 29, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maria RiusDietrich Keppler
Oct 22, 2004·Seminars in Thrombosis and Hemostasis·Meral Gunay-AygunWilliam A Gahl
Dec 31, 2005·American Journal of Human Genetics·Neil V MorganEamonn R Maher
Mar 21, 2008·Trends in Pharmacological Sciences·Frans G M RusselRosalinde Masereeuw
Dec 17, 2008·Biochemical and Biophysical Research Communications·Md Tozammel HoqueSusan P C Cole

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Citations

Apr 17, 2015·Thrombosis and Haemostasis·Andrew D MumfordDiego Mezzano
Oct 3, 2012·British Journal of Haematology·Julien Masliah-PlanchonSylvia Bellucci
Sep 1, 2015·Blood·Benoit DecouturePascale Gaussem
Oct 5, 2011·Essays in Biochemistry·Andrew J SlotSusan P C Cole
Aug 10, 2012·Platelets·Marie Lordkipanidzé
Aug 4, 2016·Hämostaseologie·Paolo GreseleLoredana Bury
Jun 24, 2017·Thrombosis Research·Wei WangYing Wang
May 10, 2018·International Journal of Laboratory Hematology·P GreseleL Bury
Jul 12, 2011·The FEBS Journal·Zhe-Sheng Chen, Amit K Tiwari
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·A Nurden, P Nurden
Jul 8, 2015·The Journal of Pharmacology and Experimental Therapeutics·Jiagen WenWei Zhang
Nov 17, 2016·Platelets·Andrea L Ambrosio, Santiago M Di Pietro
Aug 8, 2020·Journal of Clinical Medicine·Arnaud DupuisChristian Gachet
Sep 26, 2015·Blood·Satish B CheepalaJohn D Schuetz
Apr 15, 2021·Thrombosis and Haemostasis·Tiphaine Belleville-RollandChristilla Bachelot-Loza

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