Journal
JOURNAL OF IMMUNOLOGY
Volume 189, Issue 2, Pages 689-700Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1103708
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Funding
- Instituto de Salud Carlos III [PI080794, PI11/01645]
- Ministerio de Ciencia e Innovacion [SAF2008-02635, SAF2011-25834]
- Fundacion para la Investigacion y la Prevencion del SIDA en Espana [36658/07]
- Ministerio de Educacion y Ciencia [BIO2009-07990]
- Comunidad de Madrid [CAM BIO/0194/2006]
- Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Instituto Salud Carlos III) [RECAVA RD06/0014]
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EWI motif-containing protein 2 (EWI-2) is a member of the Ig superfamily that links tetraspanin-enriched microdomains to the actin cytoskeleton. We found that EWI-2 colocalizes with CD3 and CD81 at the central supramolecular activation cluster of the T cell immune synapse. Silencing of the endogenous expression or overexpression of a cytoplasmic truncated mutant of EWI-2 in T cells increases IL-2 secretion upon Ag stimulation. Mass spectrometry experiments of pull-downs with the C-term intracellular domain of EWI-2 revealed the specific association of EWI-2 with the actin-binding protein alpha-actinin; this association was regulated by PIP2. alpha-Actinin regulates the immune synapse formation and is required for efficient T cell activation. We extended these observations to virological synapses induced by HIV and found that silencing of either EWI-2 or alpha-actinin-4 increased cell infectivity. Our data suggest that the EWI-2-alpha-actinin complex is involved in the regulation of the actin cytoskeleton at T cell immune and virological synapses, providing a link between membrane microdomains and the formation of polarized membrane structures involved in T cell recognition. The Journal of Immunology, 2012, 189: 689-700.
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