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

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 Pasche, Ute Becherer, Dieter Bruns and Jens Rettig ()
Additional contact information
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

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2467

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