RhoG protein regulates platelet granule secretion and thrombus formation in mice.
J Biol Chem
; 288(47): 34217-34229, 2013 Nov 22.
Article
em En
| MEDLINE
| ID: mdl-24106270
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.
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MEDLINE
Assunto principal:
Trombose
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Coagulação Sanguínea
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Plaquetas
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Vesículas Secretórias
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GTP Fosfo-Hidrolases
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article