Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse - Institut Pasteur Access content directly
Journal Articles Journal of Experimental Medicine Year : 2013

Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse

Martin Sachse
Miguel A Alonso
  • Function : Author
Christophe Zimmer
Andrès Alcover
  • Function : Author

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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Dates and versions

pasteur-01371057 , version 1 (23-09-2016)

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Helena Soares, Ricardo Henriques, Martin Sachse, Leandro Ventimiglia, Miguel A Alonso, et al.. Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse. Journal of Experimental Medicine, 2013, 210 (11), pp.2415 - 2433. ⟨10.1084/jem.20130150⟩. ⟨pasteur-01371057⟩
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