EWI-2 association with α-actinin regulates T cell immune synapses and HIV viral infection.
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 α-actinin; this association was regulated by PIP2. α-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 α-actinin-4 increased cell infectivity. Our data suggest that the EWI-2-α-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.
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
Mónica
M
Gordón-Alonso
Mónica
M
Sala-Valdés
Vera
V
Rocha-Perugini
Daniel
D
Pérez-Hernández
Soraya
S
López-Martín
Angeles
A
Ursa
Susana
S
Alvarez
Tatiana V
TV
Kolesnikova
Jesús
J
Vázquez
Francisco
F
Sánchez-Madrid
María
M
Yáñez-Mó
D000185:Actinin / Q000378:metabolism* / Q000502:physiology; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D002461:Cell Line, Transformed; D003599:Cytoskeleton / Q000276:immunology / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology / Q000473:pathology / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C440028:IGSF8 protein, human; D008565:Membrane Proteins; D000185:Actinin