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Publication Detail
Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Soares H, Henriques R, Sachse M, Ventimiglia L, Alonso MA, Zimmer C, Thoulouze M-I, Alcover A
  • Publication date:
    21/10/2013
  • Pagination:
    2415, 2433
  • Journal:
    J Exp Med
  • Volume:
    210
  • Issue:
    11
  • Status:
    Published
  • Country:
    United States
  • PII:
    jem.20130150
  • Language:
    eng
  • Keywords:
    Adaptor Proteins, Signal Transducing, Calcium, Cell Compartmentation, Cytokines, Exocytosis, Gene Silencing, Humans, Immunological Synapses, Jurkat Cells, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Membrane Fusion, Membrane Proteins, Myelin and Lymphocyte-Associated Proteolipid Proteins, Phosphorylation, Protein Transport, Receptors, Antigen, T-Cell, Signal Transduction, Synaptotagmins, T-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase
Abstract
How the vesicular traffic of signaling molecules contributes to T cell receptor (TCR) signal transduction at the immunological synapse remains poorly understood. In this study, we show that the protein tyrosine kinase Lck, the TCRζ subunit, and the adapter LAT traffic through distinct exocytic compartments, which are released at the immunological synapse in a differentially regulated manner. Lck vesicular release depends on MAL protein. Synaptic Lck, in turn, conditions the calcium- and synaptotagmin-7-dependent fusion of LAT and TCRζ containing vesicles. Fusion of vesicles containing TCRζ and LAT at the synaptic membrane determines not only the nanoscale organization of phosphorylated TCRζ, ZAP70, LAT, and SLP76 clusters but also the presence of phosphorylated LAT and SLP76 in interacting signaling nanoterritories. This mechanism is required for priming IL-2 and IFN-γ production and may contribute to fine-tuning T cell activation breadth in response to different stimulatory conditions.
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