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Alterations in platelet alpha granule secretion and adhesion on collagen under flow in mice lacking the atypical Rho GTPase RhoBTB3

Berger, Martin; Riley, David R J; Lutz, Julia; Khalil, Jawad S; Aburima, Ahmed; Naseem, Khalid M; Rivero, Francisco

Authors

Martin Berger 10 mberger@ukaachen.de.

David R J Riley david.riley@hyms.ac.uk (DRJR), juliablutz@googlemail.com (JL)

Julia Lutz

Jawad S Khalil 8 jawad.khalil@hyms.ac.uk (JSK)

Ahmed Aburima ahmed.aburima@hyms.ac.uk (AA). 9

Khalid M Naseem

Francisco Rivero francisco.rivero@hyms.ac.uk



Abstract

Typical Rho GTPases, like 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 characterised 1 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 ADP. By contrast, alpha granule secretion was increased in mice lacking RhoBTB3 in response to thrombin, 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 haemostasis in vivo.

Journal Article Type Article
Publication Date Feb 11, 2019
Journal Cells
Print ISSN 2073-4409
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 8
Issue 2
Pages 149
APA6 Citation Berger, M., Riley, D. R. J., Lutz, J., Khalil, J. S., Aburima, A., Naseem, K. M., & Rivero, F. (2019). Alterations in platelet alpha granule secretion and adhesion on collagen under flow in mice lacking the atypical Rho GTPase RhoBTB3. Cells, 8(2), 149. https://doi.org/10.3390/cells8020149
DOI https://doi.org/10.3390/cells8020149
Keywords Adhesion; Collagen; Platelets; Rho GTPases; RhoBTB3
Publisher URL https://www.mdpi.com/2073-4409/8/2/149

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© 2019 by the authors. Submitted for possible open access publication under the terms
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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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