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  1. AU="Kemmoku, Haruka"
  2. AU="Meseguer, M"
  3. AU="Pillaye, Jayshree"
  4. AU="Andrew Pettitt"
  5. AU="Malawski, M"
  6. AU=Marhofer P
  7. AU=Mandel H G
  8. AU="Duffy, Richard"
  9. AU=Kaseb Hatem AU=Kaseb Hatem
  10. AU=Kong Tak?kwan AU=Kong Tak?kwan
  11. AU=Nagaraja Sridevi
  12. AU="Bu, Yingzi"
  13. AU=Seddighi Hamed AU=Seddighi Hamed
  14. AU="De Keyser, Johan"
  15. AU="Zhenqiang Bi"
  16. AU=Wang Jun
  17. AU=Zhang Fuping
  18. AU="Shatilov, D N"

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  1. Artikel ; Online: Specific association of TBK1 with the trans-Golgi network following STING stimulation.

    Kemmoku, Haruka / Kuchitsu, Yoshihiko / Mukai, Kojiro / Taguchi, Tomohiko

    Cell structure and function

    2022  Band 47, Heft 1, Seite(n) 19–30

    Abstract: Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA or self-DNA leaked from mitochondria/nuclei. In response to the emergence of such DNAs in the cytosol, STING relocates from the endoplasmic ... ...

    Abstract Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA or self-DNA leaked from mitochondria/nuclei. In response to the emergence of such DNAs in the cytosol, STING relocates from the endoplasmic reticulum (ER) to the Golgi, and activates TANK-binding kinase 1 (TBK1), a cytosolic kinase essential for the activation of STING-dependent downstream signalling. To understand at which subcellular compartments TBK1 becomes associated with STING, we generated cells stably expressing fluorescent protein-tagged STING (mNeonGreen-STING) and TBK1 (TBK1-mScarletI). We found that after STING stimulation, TBK1 became associated with the trans-Golgi network (TGN), not the other parts of the Golgi. STING variants that constitutively induce the type I interferon response have been identified in patients with autoinflammatory diseases named "STING-associated vasculopathy with onset in infancy (SAVI)". Even in cells expressing these constitutively active STING variants, TBK1 was found to be associated with TGN, not the other parts of the Golgi. These results suggest that TGN acts as a specific platform where STING associates with and activates TBK1.Key words: the Golgi, membrane traffic, innate immunity, STING.
    Mesh-Begriff(e) Endoplasmic Reticulum ; Golgi Apparatus ; Humans ; Immunity, Innate ; Membrane Proteins/genetics ; Protein Serine-Threonine Kinases/genetics ; Signal Transduction ; trans-Golgi Network
    Chemische Substanzen Membrane Proteins ; STING1 protein, human ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TBK1 protein, human (EC 2.7.11.1)
    Sprache Englisch
    Erscheinungsdatum 2022-02-05
    Erscheinungsland Japan
    Dokumenttyp Journal Article
    ZDB-ID 197293-5
    ISSN 1347-3700 ; 0386-7196
    ISSN (online) 1347-3700
    ISSN 0386-7196
    DOI 10.1247/csf.21080
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol.

    Kemmoku, Haruka / Takahashi, Kanoko / Mukai, Kojiro / Mori, Toshiki / Hirosawa, Koichiro M / Kiku, Fumika / Uchida, Yasunori / Kuchitsu, Yoshihiko / Nishioka, Yu / Sawa, Masaaki / Kishimoto, Takuma / Tanaka, Kazuma / Yokota, Yasunari / Arai, Hiroyuki / Suzuki, Kenichi G N / Taguchi, Tomohiko

    Nature communications

    2024  Band 15, Heft 1, Seite(n) 220

    Abstract: Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol. STING may function as a scaffold to activate TANK-binding kinase 1 (TBK1), but direct cellular evidence remains lacking. ...

    Abstract Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived DNA in the cytosol. STING may function as a scaffold to activate TANK-binding kinase 1 (TBK1), but direct cellular evidence remains lacking. Here we show, using single-molecule imaging of STING with enhanced time resolutions down to 5 ms, that STING becomes clustered at the trans-Golgi network (about 20 STING molecules per cluster). The clustering requires STING palmitoylation and the Golgi lipid order defined by cholesterol. Single-molecule imaging of TBK1 reveals that STING clustering enhances the association with TBK1. We thus provide quantitative proof-of-principle for the signaling STING scaffold, reveal the mechanistic role of STING palmitoylation in the STING activation, and resolve the long-standing question of the requirement of STING translocation for triggering the innate immune signaling.
    Mesh-Begriff(e) trans-Golgi Network/metabolism ; Lipoylation ; Microscopy ; Single Molecule Imaging ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Cholesterol ; Cluster Analysis ; Immunity, Innate
    Chemische Substanzen Membrane Proteins ; Cholesterol (97C5T2UQ7J)
    Sprache Englisch
    Erscheinungsdatum 2024-01-11
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44317-5
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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