Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3
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 ar...
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MDPI AG
2019-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/2/149 |
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| author | Martin Berger David R. J. Riley Julia Lutz Jawad S. Khalil Ahmed Aburima Khalid M. Naseem Francisco Rivero |
| author_facet | Martin Berger David R. J. Riley Julia Lutz Jawad S. Khalil Ahmed Aburima Khalid M. Naseem Francisco Rivero |
| author_sort | Martin Berger |
| collection | DOAJ |
| description | 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 <i>Rhobtb3</i> 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 <i>Rho</i><i>btb</i><i>3</i> leads to subtle alterations in alpha-granule secretion and adhesion to collagen without significant effects on hemostasis in vivo. |
| first_indexed | 2024-03-12T19:21:43Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:21:43Z |
| publishDate | 2019-02-01 |
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| series | Cells |
| spelling | doaj.art-449064c5ca934e64a3ee839f9cf792672023-08-02T05:05:42ZengMDPI AGCells2073-44092019-02-018214910.3390/cells8020149cells8020149Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3Martin Berger0David R. J. Riley1Julia Lutz2Jawad S. Khalil3Ahmed Aburima4Khalid M. Naseem5Francisco Rivero6Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UKCentre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UKCentre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UKCentre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UKCentre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UKLeeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, LS2 9NL Leeds, UKCentre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, HU6 7RX Hull, UKTypical 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 <i>Rhobtb3</i> 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 <i>Rho</i><i>btb</i><i>3</i> leads to subtle alterations in alpha-granule secretion and adhesion to collagen without significant effects on hemostasis in vivo.https://www.mdpi.com/2073-4409/8/2/149adhesioncollagenplateletsRho GTPasesRhoBTB3 |
| spellingShingle | Martin Berger David R. J. Riley Julia Lutz Jawad S. Khalil Ahmed Aburima Khalid M. Naseem Francisco Rivero Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3 Cells adhesion collagen platelets Rho GTPases RhoBTB3 |
| title | Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3 |
| title_full | Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3 |
| title_fullStr | Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3 |
| title_full_unstemmed | Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3 |
| title_short | Alterations in Platelet Alpha-Granule Secretion and Adhesion on Collagen under Flow in Mice Lacking the Atypical Rho GTPase RhoBTB3 |
| title_sort | alterations in platelet alpha granule secretion and adhesion on collagen under flow in mice lacking the atypical rho gtpase rhobtb3 |
| topic | adhesion collagen platelets Rho GTPases RhoBTB3 |
| url | https://www.mdpi.com/2073-4409/8/2/149 |
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