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Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion

Author

Listed:
  • Ulf Matti

    (Saarland University)

  • Varsha Pattu

    (Saarland University)

  • Mahantappa Halimani

    (Saarland University)

  • Claudia Schirra

    (Saarland University)

  • Elmar Krause

    (Saarland University)

  • Yuanyuan Liu

    (Saarland University)

  • Lisa Weins

    (Saarland University)

  • Hsin Fang Chang

    (Saarland University)

  • Raul Guzman

    (Saarland University)

  • Jenny Olausson

    (Saarland University)

  • Marc Freichel

    (Saarland University)

  • Frank Schmitz

    (Saarland University)

  • Mathias Pasche

    (Saarland University)

  • Ute Becherer

    (Saarland University)

  • Dieter Bruns

    (Saarland University)

  • Jens Rettig

    (Saarland University)

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.

Suggested Citation

  • Ulf Matti & Varsha Pattu & Mahantappa Halimani & Claudia Schirra & Elmar Krause & Yuanyuan Liu & Lisa Weins & Hsin Fang Chang & Raul Guzman & Jenny Olausson & Marc Freichel & Frank Schmitz & Mathias P, 2013. "Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion," Nature Communications, Nature, vol. 4(1), pages 1-8, June.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2467
    DOI: 10.1038/ncomms2467
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    Cited by:

    1. Hsin-Fang Chang & Claudia Schirra & Momchil Ninov & Ulrike Hahn & Keerthana Ravichandran & Elmar Krause & Ute Becherer & Štefan Bálint & Maria Harkiolaki & Henning Urlaub & Salvatore Valitutti & Cosim, 2022. "Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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