title: Syntaxin7 is required for lytic granule release from cytotoxic T lymphocytes.
abstract: SNARE proteins are essential fusion mediators for many intracellular trafficking events. Here, we investigate the role of Syntaxin7 (Stx7) in the release of lytic granules from cytotoxic T lymphocytes (CTLs). We show that Stx7 is expressed in CTLs and is preferentially localized to the region of lytic granule release, the immunological synapse (IS). Interference of Stx7 function by expression of a dominant-negative Stx7 construct or by small interfering RNA leads to a dramatic reduction of CTL-mediated killing of target cells. Real-time visualization of individual lytic granules at the IS by evanescent wave microscopy reveals that lytic granules in Stx7-deprived CTLs not only fail to fuse with the plasma membrane but even fail to accumulate at the IS. Surprisingly, the accumulation defect is not caused by an overall reduction in lytic granule number, but by a defect in the trafficking of T cell receptors (TCRs) through endosomes. Subsequent high-resolution nanoscopy shows that Stx7 colocalizes with Rab7 on late endosomes. We conclude from these data that the accumulation of recycling TCRs at the IS is a SNARE-dependent process and that Stx7-mediated processing of recycling TCRs through endosomes is a prerequisite for the cytolytic function of CTLs.
authors: Institut für Physiologie, Universität des Saarlandes, Kirrberger Straße 8, Gebäude 59, 66421 Homburg, Saarland, Germany.
authors: Varsha
authors: V
authors: Pattu
authors: Bin
authors: B
authors: Qu
authors: Misty
authors: M
authors: Marshall
authors: Ute
authors: U
authors: Becherer
authors: Christian
authors: C
authors: Junker
authors: Ulf
authors: U
authors: Matti
authors: Eva C
authors: EC
authors: Schwarz
authors: Elmar
authors: E
authors: Krause
authors: Markus
authors: M
authors: Hoth
authors: Jens
authors: J
authors: Rettig
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis / Q000276:immunology / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses / Q000502:physiology; D008213:Lymphocyte Activation; D008561:Membrane Fusion / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell