title: Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion.
abstract: Cytotoxic T lymphocytes kill virus-infected and tumorigenic target cells through the release of perforin and granzymes via fusion of lytic granules at the contact site, the immunological synapse. It has been postulated that this fusion process is mediated by non-neuronal members of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex protein family. Here, using a synaptobrevin2-monomeric red fluorescence protein knock-in mouse we demonstrate that, surprisingly, the major neuronal v-SNARE synaptobrevin2 is expressed in cytotoxic T lymphocytes and exclusively localized on granzyme B-containing lytic granules. Cleavage of synaptobrevin2 by tetanus toxin or ablation of the synaptobrevin2 gene leads to a complete block of lytic granule exocytosis while leaving upstream events unaffected, identifying synaptobrevin2 as the v-SNARE responsible for the fusion of lytic granules at the immunological synapse.
authors: Department of Physiology, Saarland University, Building 59, 66421 Homburg, Germany.
authors: Ulf
authors: U
authors: Matti
authors: Varsha
authors: V
authors: Pattu
authors: Mahantappa
authors: M
authors: Halimani
authors: Claudia
authors: C
authors: Schirra
authors: Elmar
authors: E
authors: Krause
authors: Yuanyuan
authors: Y
authors: Liu
authors: Lisa
authors: L
authors: Weins
authors: Hsin Fang
authors: HF
authors: Chang
authors: Raul
authors: R
authors: Guzman
authors: Jenny
authors: J
authors: Olausson
authors: Marc
authors: M
authors: Freichel
authors: Frank
authors: F
authors: Schmitz
authors: Mathias
authors: M
authors: Pasche
authors: Ute
authors: U
authors: Becherer
authors: Dieter
authors: D
authors: Bruns
authors: Jens
authors: J
authors: Rettig
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015550:Cell Degranulation / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D054992:Immunological Synapses / Q000187:drug effects / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013744:Tetanus Toxin / Q000494:pharmacology; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; D013744:Tetanus Toxin; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse; D049452:Green Fluorescent Proteins
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