Dynamin-related protein-1 controls fusion pore dynamics during platelet granule exocytosis.
Arterioscler Thromb Vasc Biol
; 33(3): 481-8, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23288151
ABSTRACT
OBJECTIVE:
Platelet granule exocytosis serves a central role in hemostasis and thrombosis. Recently, single-cell amperometry has shown that platelet membrane fusion during granule exocytosis results in the formation of a fusion pore that subsequently expands to enable the extrusion of granule contents. However, the molecular mechanisms that control platelet fusion pore expansion and collapse are not known. METHODS ANDRESULTS:
We identified dynamin-related protein-1 (Drp1) in platelets and found that an inhibitor of Drp1, mdivi-1, blocked exocytosis of both platelet dense and α-granules. We used single-cell amperometry to monitor serotonin release from individual dense granules and, thereby, measured the effect of Drp1 inhibition on fusion pore dynamics. Inhibition of Drp1 increased spike width and decreased prespike foot events, indicating that Drp1 influences fusion pore formation and expansion. Platelet-mediated thrombus formation in vivo after laser-induced injury of mouse cremaster arterioles was impaired after infusion of mdivi-1.CONCLUSIONS:
These results demonstrate that inhibition of Drp1 disrupts platelet fusion pore dynamics and indicate that Drp1 can be targeted to control thrombus formation in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Trombose
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Plaquetas
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Vesículas Secretórias
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Proteínas Mitocondriais
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Dinaminas
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Exocitose
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Lesões do Sistema Vascular
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GTP Fosfo-Hidrolases
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Fusão de Membrana
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Proteínas Associadas aos Microtúbulos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article