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Cells 2019, 8(2), 149; https://doi.org/10.3390/cells8020149

Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3

1
Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UK
2
Department of Internal Medicine 1, University Hospital, RWTH Aachen, 52074 Aachen, Germany
3
Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, LS2 9NL Leeds, UK
*
Author to whom correspondence should be addressed.
Received: 8 January 2019 / Revised: 31 January 2019 / Accepted: 7 February 2019 / Published: 11 February 2019
(This article belongs to the Section Cell Motility and Adhesion)
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Abstract

Typical Rho GTPases, such as Rac1, Cdc42, and RhoA, act as molecular switches regulating various aspects of platelet cytoskeleton reorganization. The loss of these enzymes results in reduced platelet functionality. Atypical Rho GTPases of the RhoBTB subfamily are characterized by divergent domain architecture. One family member, RhoBTB3, is expressed in platelets, but its function is unclear. In the present study we examined the role of RhoBTB3 in platelet function using a knockout mouse model. We found the platelet count, size, numbers of both alpha and dense granules, and surface receptor profile in these mice were comparable to wild-type mice. Deletion of Rhobtb3 had no effect on aggregation and dense granule secretion in response to a range of agonists including thrombin, collagen, and adenosine diphosphate (ADP). By contrast, alpha-granule secretion increased in mice lacking RhoBTB3 in response to thrombin, collagen related peptide (CRP) and U46619/ADP. Integrin activation and spreading on fibrinogen and collagen under static conditions were also unimpaired; however, we observed reduced platelet accrual on collagen under flow conditions. These defects did not translate into alterations in tail bleeding time. We conclude that genetic deletion of Rhobtb3 leads to subtle alterations in alpha-granule secretion and adhesion to collagen without significant effects on hemostasis in vivo. View Full-Text
Keywords: adhesion; collagen; platelets; Rho GTPases; RhoBTB3 adhesion; collagen; platelets; Rho GTPases; RhoBTB3
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Berger, M.; Riley, D.R.J.; Lutz, J.; Khalil, J.S.; Aburima, A.; Naseem, K.M.; Rivero, F. Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3. Cells 2019, 8, 149.

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