Åbrink, Magnus
- Uppsala University
Abstract
The Rab27 GTPase subfamily consists of two closely related homologs, Rab27a and Rab27b. Rab27a has been shown previously to regulate organelle movement and regulated exocytosis in a wide variety of secretory cells. However, the role of the more restrictedly expressed Rab27b remains unclear. Here we describe the creation of Rab27b knockout (KO) strain that was subsequently crossed with the naturally occurring Rab27a KO line, ashen, to produce double KO (Rab27a(ash/ash) Rab27b(-/-)) mice. Rab27b KO (and double KO) exhibit significant hemorrhagic disease in contrast to ashen mice. In vitro assays demonstrated impaired aggregation with collagen and U46619 and reduced secretion of dense granules in both Rab27b and double KO strains. Additionally, we detected a 50% reduction in the number of dense granules per platelet and diminished platelet serotonin content, possibly due to a dense granule packaging defect into proplatelets during megakaryocyte maturation. The presence of Rab27a partially compensated for the secretory defect but not the reduced granule number. The morphology and function of platelet alpha-granules were unaffected. our data suggest that Rab27b is a key regulator of dense granule secretion in platelets and thus a candidate gene for delta-storage pool deficiency in humans.
Keywords
membrane traffic; Rab GTPase
Published in
Proceedings of the National Academy of Sciences
2007, volume: 104, number: 14, pages: 5872-5877
Publisher: NATL ACAD SCIENCES
SLU Authors
UKÄ Subject classification
Biochemistry
Cell Biology
Molecular Biology
Publication identifier
- DOI: https://doi.org/10.1073/pnas.0609879104
Permanent link to this page (URI)
https://res.slu.se/id/publ/41365