Syntaxin 8 is required for efficient lytic granule trafficking in cytotoxic T lymphocytes

Publication date: July 2016 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1863, Issue 7, Part A Author(s): Shruthi S. Bhat, Kim S. Friedmann, Arne Knörck, Cora Hoxha, Petra Leidinger, Christina Backes, Eckart Meese, Andreas Keller, Jens Rettig, Markus Hoth, Bin Qu, Eva C. Schwarz Cytotoxic T lymphocytes (CTL) eliminate pathogen-infected and cancerous cells mainly by polarized secretion of lytic granules (LG, containing cytotoxic molecules like perforin and granzymes) at the immunological synapse (IS). Members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family are involved in trafficking (generation, transport and fusion) of vesicles at the IS. Syntaxin 8 (Stx8) is expressed in LG and colocalizes with the T cell receptor (TCR) upon IS formation. Here, we report the significance of Stx8 for human CTL cytotoxicity. We found that Stx8 mostly localized in late, recycling endosomal and lysosomal compartments with little expression in early endosomal compartments. Down-regulation of Stx8 by siRNA resulted in reduced cytotoxicity. We found that following perforin release of the pre-existing pool upon target cell contact, Stx8 down-regulated CTL regenerate perforin pools less efficiently and thus release less perforin compared to control CTL. CD107a degranulation, real-time and end-point population cytotoxicity assays, and high resolution microscopy support our conclusion that Stx8 is ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research