Journal of Biological Chemistry
Volume 288, Issue 47, 22 November 2013, Pages 34217-34229
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Cell Biology
RhoG Protein Regulates Platelet Granule Secretion and Thrombus Formation in Mice*

https://doi.org/10.1074/jbc.M113.504100Get rights and content
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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.

Platelets
Proteomics
Rho GTPases
Secretion
Thrombosis
Transgenic Mice

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*

This work was supported by Wellcome Trust Clinical Research Training Fellowship Award WT090093MA (to R. G., H. M., and A. W. P.). British Heart Foundation grants (to A. W. P.) supported M. T. H. and C. M. W. (Grant RG/10/006/28299) and J. S. S. (Grant RG/05/083), and Medical Research Council Grant G1000432 (to Stuart Mundell) supported R. J. P.

This article contains supplemental Data A–C.

1

These authors contributed equally to this work.