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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Published in:	Cells (Basel, Switzerland) Vol. 8; no. 2; p. 149
Main Authors:	Berger, Martin, Lutz, David R J, Lutz, Julia, Khalil, Jawad S, Aburima, Ahmed, Naseem, Khalid M, Rivero, Francisco
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 11-02-2019 MDPI
Subjects:	Adenosine adhesion Animals Blood clots Blood platelets Blood Platelets - drug effects Blood Platelets - metabolism Blood Platelets - ultrastructure Cdc42 protein Cell cycle Cell Line Collagen Collagen - pharmacology Cytokines Cytoplasmic Granules - drug effects Cytoplasmic Granules - metabolism Cytoskeleton Experiments Fibrinogen Guanosine triphosphatases Hemostasis Humans Megakaryocytes - drug effects Megakaryocytes - metabolism Mice, Inbred C57BL Mice, Knockout Microscopy Platelet Adhesiveness - drug effects Platelet Aggregation - drug effects Platelet Glycoprotein GPIIb-IIIa Complex - metabolism Platelets Proteins Rac1 protein Regulation Rheology rho GTP-Binding Proteins - deficiency rho GTP-Binding Proteins - genetics rho GTP-Binding Proteins - metabolism Rho GTPases RhoA protein RhoBTB3 RNA, Messenger - genetics RNA, Messenger - metabolism Secretion Thrombin United Kingdom > UK United States > US Japan Germany collagen Rho GTPases adhesion RhoBTB3 platelets
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Summary:	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 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 leads to subtle alterations in alpha-granule secretion and adhesion to collagen without significant effects on hemostasis in vivo.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells8020149