A role for glycosphingolipid-enriched microdomains in platelet glycoprotein Ib-mediated platelet activation.
J Thromb Haemost
; 5(5): 1034-40, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17461932
ABSTRACT
BACKGROUND:
Glycoprotein (GP) Ib, a platelet von Willebrand factor (VWF) receptor, plays a crucial role in thrombosis and hemostasis. As recent reports have suggested that GPIb partially locates in a particular region, designated as glycosphingolipid-enriched microdomains (GEMs), we hypothesized that GEMs play a central role in GPIb-mediated platelet activation.METHODS:
Platelets were stimulated by VWF/botrocetin to activate platelets through GPIb. GEMs and non-GEMs were isolated by sucrose density gradient ultracentrifugation and the location of signaling molecules characterized. The role of GEMs-mediated signaling in platelet behavior was tested by platelet aggregation and by platelet interaction with immobilized VWF under flow conditions when GEMs were disrupted by methyl-beta-cyclodextrin (MbetaCD).RESULTS:
GPIb was partially translocated to GEMs upon VWF/botrocetin stimulation. Immunoprecipitation of GPIb in GEMs and non-GEMs revealed that the tyrosine kinases, Src and Lyn, were associated with GPIb only in GEMs after GPIb-stimulation, and not in non-GEMs. Activation of PLCgamma2 was more intense in GEMs than non-GEMs. Disruption of GEMs by MbetaCD strongly inhibited tyrosine phosphorylation of Syk and PLCgamma2. Functional studies revealed that stable adhesion of platelets to a VWF-coated surface under flow was impaired by GEM disruption by MbetaCD.CONCLUSION:
The combined results suggest that GEMs play an important role in GPIb-mediated platelet activation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoesfingolipídeos
/
Ativação Plaquetária
/
Complexo Glicoproteico GPIb-IX de Plaquetas
Limite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão