Cdc42 and the Rho GEF intersectin-1 collaborate with Nck to promote N-WASP-dependent actin polymerisation.
J Cell Sci
; 127(Pt 3): 673-85, 2014 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-24284073
ABSTRACT
Vaccinia virus enhances its cell-to-cell spread by inducing Arp2/3-dependent actin polymerisation. This process is initiated by Src- and Abl-mediated phosphorylation of the viral transmembrane protein A36, leading to recruitment of a signalling network consisting of Grb2, Nck, WIP and N-WASP. Nck is a potent activator of N-WASP-Arp2/3-dependent actin polymerisation. However, recent observations demonstrate that an interaction between Nck and N-WASP is not required for vaccinia actin tail formation. We found that Cdc42 cooperates with Nck to promote actin tail formation by stabilising N-WASP beneath the virus. Cdc42 activation is mediated by the Rho guanine-nucleotide-exchange factor (GEF) intersectin-1 (ITSN1), which is recruited to the virus prior to its actin-based motility. Moreover, Cdc42, ITSN1 and N-WASP function collaboratively in a feed-forward loop to promote vaccinia-induced actin polymerisation. Outside the context of infection, we demonstrate that ITSN1 also functions together with Cdc42, Nck and N-WASP during phagocytosis mediated by the Fc gamma receptor. Our observations suggest that ITSN1 is an important general regulator of Cdc42-, Nck- and N-WASP-dependent actin polymerisation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus Vaccinia
/
Actinas
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Proteínas Oncogénicas
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Proteína de Unión al GTP cdc42
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Proteínas Adaptadoras del Transporte Vesicular
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Proteínas Adaptadoras Transductoras de Señales
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Proteína Neuronal del Síndrome de Wiskott-Aldrich
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido