A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton.
J Clin Invest
; 126(10): 3837-3851, 2016 10 03.
Article
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| MEDLINE
| ID: mdl-27599296
ABSTRACT
Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor-driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that links TCRs to the actin cytoskeleton in TCR-driven actin assembly. Further, they provide an explanation for similarities in the clinical phenotypes of WAS and DOCK8 deficiency.
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1
Base de datos:
MEDLINE
Asunto principal:
Citoesqueleto de Actina
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Receptores de Antígenos de Linfocitos T
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Proteínas Portadoras
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Factores de Intercambio de Guanina Nucleótido
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Proteína del Síndrome de Wiskott-Aldrich
Idioma:
En
Revista:
J Clin Invest
Año:
2016
Tipo del documento:
Article