کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10801671 | 1055628 | 2016 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Syntaxin 8 is required for efficient lytic granule trafficking in cytotoxic T lymphocytes
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کلمات کلیدی
CTLEffector to target ratioLytic granulesFHLCHXqRT-PCRHLHE:T - E: TStaphylococcal enterotoxin A - انتروتوکسین استافیلوکوک ASea - دریاییImmunological synapse - سیناپس ایمونولوژیکcycloheximide - سیکلوهایسیمیدlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Cytotoxic T lymphocytes - لنفوسیت های T سیتوتوکسیکHemophagocytic lymphohistiocytosis - لنفوهیستسیتوز هموفوگوسیتیکquantitative real time polymerase chain reaction - واکنش زنجیره ای پلیمراز واقعی در زمان واقعی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Syntaxin 8 is required for efficient lytic granule trafficking in cytotoxic T lymphocytes Syntaxin 8 is required for efficient lytic granule trafficking in cytotoxic T lymphocytes](/preview/png/10801671.png)
چکیده انگلیسی
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 required for proper and timely sorting and trafficking of cytotoxic molecules to functional LG through the endosomal pathway in human CTL.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 7, Part A, July 2016, Pages 1653-1664
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 7, Part A, July 2016, Pages 1653-1664
نویسندگان
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,