NDLI: RhoG Protein Regulates Platelet Granule Secretion and Thrombus Formation in $Mice^{*}$

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RhoG Protein Regulates Platelet Granule Secretion and Thrombus Formation in $Mice^{*}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Savage, Joshua S. Harper, Matthew T. Mundell, Stuart J. Heesom, Kate J. Poole, Alastair W. Williams, Christopher M. Mellor, Harry Pope, Robert J. Bass, Mark Goggs, Robert
Description	Author Affiliation: Goggs R ( From the School of Physiology and Pharmacology.)
Abstract	Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used $RhoG^{−/−}$ mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in $RhoG^{−/−}$ platelets stimulated by CRP, but responses to thrombin were normal. The central defect in $RhoG^{−/−}$ platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in $RhoG^{−/−}$ platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in $RhoG^{−/−}$ mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	47
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-11-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Blood Coagulation Blood Platelets Enzymology GTP Phosphohydrolases Metabolism Secretory Vesicles Secretion Thrombosis Adenosine Diphosphate Pharmacology Animals Pathology Carrier Proteins Genetics Hemostatics Mice Mice, Knockout Peptides Platelet Activation Drug Effects Thrombin Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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