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

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.

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), Article 149. https://doi.org/10.3390/cells8020149

• Journal Article Type: Article
• Acceptance Date: Feb 7, 2019
• Online Publication Date: Feb 11, 2019
• Publication Date: Feb 1, 2019
• Deposit Date: Feb 7, 2019
• Publicly Available Date: Feb 8, 2019
• Journal: Cells
• Electronic ISSN: 2073-4409
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 2
• Article Number: 149
• DOI: https://doi.org/10.3390/cells8020149
• Keywords: Adhesion; Collagen; Platelets; Rho GTPases; RhoBTB3
• Public URL: https://hull-repository.worktribe.com/output/1282572
• Publisher URL: https://www.mdpi.com/2073-4409/8/2/149
• Contract Date: Feb 7, 2019