The role of Rab38 in platelet dense granule defects.
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.


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.
Ninkovic
I
I
Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
White
J G
JG
Rangel-Filho
A
A
Datta
Y H
YH
D000818:Animals; D001792:Blood Platelets / Q000473:pathology*; D015153:Blotting, Western; D003594:Cytoplasmic Granules / Q000473:pathology*; D008533:Megakaryocytes; D009154:Mutation; D010981:Platelet Storage Pool Deficiency / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D051381:Rats; D012701:Serotonin / Q000032:analysis; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D012701:Serotonin; C498787:Rab38 protein, rat; D020691:rab GTP-Binding Proteins