The role of Rab38 in platelet dense granule defects

I. Ninkovic, J. G. White, A. Rangel-Filho, Yvonne H. Datta

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: The fawn-hooded hypertensive (FHH) rat has a mutation in the Rab38 gene that is associated with a platelet dense granule storage pool disease. Objective: To better characterize the expression and function of Rab38 in FHH rat and human megakaryocytes and platelets. Patients and methods: Rab38 expression in FHH rat and normal tissues was demonstrated by western blotting. Platelet and megakaryocyte morphology and Rab38 expression were examined by transmission electron microscopy and by immunofluorescence confocal microscopy. Platelet surface glycoprotein and P-selectin expression and total serotonin content were assessed by flow cytometry. Results: Rab38 was not expressed in FHH rat tissues, and FHH rat platelets and megakaryocytes lacked dense granules. FHH rat platelets had normal expression of surface glycoproteins and of surface P-selectin in response to thrombin. The total serotonin content in FHH rat platelets was similar to that in Brown Norway rat platelets. In a megakaryocyte cell line, Rab38 was expressed in a granular perinuclear and cytoplasmic pattern. There was partial colocalization with serotonin, and minimal colocalization with von Willebrand factor and lysosomal proteins. Conclusions: The lack of Rab38 expression in the FHH rat results in the absence of normal dense granules in the megakaryocytes and platelets, which have otherwise normal structure and function. Rab38 may play a role in the development of dense granules in the megakaryocytes and platelets.

Original languageEnglish (US)
Pages (from-to)2143-2151
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Megakaryocytes
Blood Platelets
Serotonin
P-Selectin
Membrane Glycoproteins
von Willebrand Factor
Platelet Membrane Glycoproteins
Transmission Electron Microscopy
Fluorescence Microscopy
Confocal Microscopy
Thrombin
Flow Cytometry
Western Blotting
Cell Line
Mutation
Genes

Keywords

  • Dense granule
  • Megakaryocyte
  • Platelet function defect
  • Platelets
  • Rab38
  • Rat

ASJC Scopus subject areas

  • Hematology

Cite this

Ninkovic, I., White, J. G., Rangel-Filho, A., & Datta, Y. H. (2008). The role of Rab38 in platelet dense granule defects. Journal of Thrombosis and Haemostasis, 6(12), 2143-2151. https://doi.org/10.1111/j.1538-7836.2008.03178.x

The role of Rab38 in platelet dense granule defects. / Ninkovic, I.; White, J. G.; Rangel-Filho, A.; Datta, Yvonne H.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 12, 2008, p. 2143-2151.

Research output: Contribution to journalArticle

Ninkovic, I, White, JG, Rangel-Filho, A & Datta, YH 2008, 'The role of Rab38 in platelet dense granule defects', Journal of Thrombosis and Haemostasis, vol. 6, no. 12, pp. 2143-2151. https://doi.org/10.1111/j.1538-7836.2008.03178.x
Ninkovic, I. ; White, J. G. ; Rangel-Filho, A. ; Datta, Yvonne H. / The role of Rab38 in platelet dense granule defects. In: Journal of Thrombosis and Haemostasis. 2008 ; Vol. 6, No. 12. pp. 2143-2151.
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