IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29946-6.html
   My bibliography  Save this article

Deficiency in coatomer complex I causes aberrant activation of STING signalling

Author

Listed:
  • Annemarie Steiner

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne
    Institute of Structural Biology, University Hospital Bonn)

  • Katja Hrovat-Schaale

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Ignazia Prigione

    (Centre for Autoinflammatory Diseases and Primary Immunodeficiencies, IRCCS Istituto Giannina Gaslini)

  • Chien-Hsiung Yu

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Pawat Laohamonthonkul

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Cassandra R. Harapas

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Ronnie Ren Jie Low

    (University of Melbourne
    Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research)

  • Dominic Nardo

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    Monash Biomedicine Discovery Institute, Monash University)

  • Laura F. Dagley

    (University of Melbourne
    Advanced Technology and Biology, The Walter and Eliza Hall Institute of Medical Research)

  • Michael J. Mlodzianoski

    (Center for Dynamic Imaging, The Walter and Eliza Hall Institute of Medical Research)

  • Kelly L. Rogers

    (Center for Dynamic Imaging, The Walter and Eliza Hall Institute of Medical Research)

  • Thomas Zillinger

    (Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn
    Institute of Immunology, Philipps-University Marburg, BMFZ)

  • Gunther Hartmann

    (Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn
    German Centre for Infection Research (DZIF), partner site Bonn-Cologne)

  • Michael P. Gantier

    (Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research
    Monash University)

  • Marco Gattorno

    (Centre for Autoinflammatory Diseases and Primary Immunodeficiencies, IRCCS Istituto Giannina Gaslini)

  • Matthias Geyer

    (Institute of Structural Biology, University Hospital Bonn)

  • Stefano Volpi

    (Centre for Autoinflammatory Diseases and Primary Immunodeficiencies, IRCCS Istituto Giannina Gaslini
    University of Genoa)

  • Sophia Davidson

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Seth L. Masters

    (Inflammation Division, The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

Abstract

Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within Golgi compartments. Deficiency in subunit alpha causes COPA syndrome and is associated with type I IFN signalling, although the upstream innate immune sensor involved was unknown. Using in vitro models we find aberrant activation of the STING pathway due to deficient retrograde but probably not intra-Golgi transport. Further we find the upstream cytosolic DNA sensor cGAS as essentially required to drive type I IFN signalling. Genetic deletion of COPI subunits COPG1 or COPD similarly induces type I IFN activation in vitro, which suggests that inflammatory diseases associated with mutations in other COPI subunit genes may exist. Finally, we demonstrate that inflammation in COPA syndrome patient peripheral blood mononuclear cells and COPI-deficient cell lines is ameliorated by treatment with the small molecule STING inhibitor H-151, suggesting targeted inhibition of the cGAS/STING pathway as a promising therapeutic approach.

Suggested Citation

  • Annemarie Steiner & Katja Hrovat-Schaale & Ignazia Prigione & Chien-Hsiung Yu & Pawat Laohamonthonkul & Cassandra R. Harapas & Ronnie Ren Jie Low & Dominic Nardo & Laura F. Dagley & Michael J. Mlodzia, 2022. "Deficiency in coatomer complex I causes aberrant activation of STING signalling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29946-6
    DOI: 10.1038/s41467-022-29946-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29946-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-29946-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Xiang Gui & Hui Yang & Tuo Li & Xiaojun Tan & Peiqing Shi & Minghao Li & Fenghe Du & Zhijian J. Chen, 2019. "Autophagy induction via STING trafficking is a primordial function of the cGAS pathway," Nature, Nature, vol. 567(7747), pages 262-266, March.
    2. Kojiro Mukai & Emari Ogawa & Rei Uematsu & Yoshihiko Kuchitsu & Fumika Kiku & Takefumi Uemura & Satoshi Waguri & Takehiro Suzuki & Naoshi Dohmae & Hiroyuki Arai & Anthony K. Shum & Tomohiko Taguchi, 2021. "Homeostatic regulation of STING by retrograde membrane traffic to the ER," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    3. Hiroki Ishikawa & Zhe Ma & Glen N. Barber, 2009. "STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity," Nature, Nature, vol. 461(7265), pages 788-792, October.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Maximilian Hirschenberger & Alice Lepelley & Ulrich Rupp & Susanne Klute & Victoria Hunszinger & Lennart Koepke & Veronika Merold & Blaise Didry-Barca & Fanny Wondany & Tim Bergner & Tatiana Moreau & , 2023. "ARF1 prevents aberrant type I interferon induction by regulating STING activation and recycling," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    2. Matteo Gentili & Bingxu Liu & Malvina Papanastasiou & Deborah Dele-Oni & Marc A. Schwartz & Rebecca J. Carlson & Aziz M. Al’Khafaji & Karsten Krug & Adam Brown & John G. Doench & Steven A. Carr & Nir , 2023. "ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Haruka Kemmoku & Kanoko Takahashi & Kojiro Mukai & Toshiki Mori & Koichiro M. Hirosawa & Fumika Kiku & Yasunori Uchida & Yoshihiko Kuchitsu & Yu Nishioka & Masaaki Sawa & Takuma Kishimoto & Kazuma Tan, 2024. "Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Jing Liu & Xia Bu & Chen Chu & Xiaoming Dai & John M. Asara & Piotr Sicinski & Gordon J. Freeman & Wenyi Wei, 2023. "PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Hongwei Lv & Qianni Zong & Cian Chen & Guishuai Lv & Wei Xiang & Fuxue Xing & Guoqing Jiang & Bing Yan & Xiaoyan Sun & Yue Ma & Liang Wang & Zixin Wu & Xiuliang Cui & Hongyang Wang & Wen Yang, 2024. "TET2-mediated tumor cGAS triggers endothelial STING activation to regulate vasculature remodeling and anti-tumor immunity in liver cancer," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    6. Katelyn C. Cook & Elene Tsopurashvili & Jason M. Needham & Sunnie R. Thompson & Ileana M. Cristea, 2022. "Restructured membrane contacts rewire organelles for human cytomegalovirus infection," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Lei Gao & Fushun Liu & Ruilian Liu, 2023. "The Mechanism of Aerobic Exercise Regulating the PI3K/Akt-mTOR Signaling Pathway Intervenes in Hippocampal Neuronal Apoptosis in Vascular Dementia Rats," IJERPH, MDPI, vol. 20(3), pages 1-10, January.
    8. Jeremy J. Ratiu & William E. Barclay & Elliot Lin & Qun Wang & Sebastian Wellford & Naren Mehta & Melissa J. Harnois & Devon DiPalma & Sumedha Roy & Alejandra V. Contreras & Mari L. Shinohara & David , 2022. "Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Alex J. Pollock & Shivam A. Zaver & Joshua J. Woodward, 2020. "A STING-based biosensor affords broad cyclic dinucleotide detection within single living eukaryotic cells," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    10. Maximilian Hirschenberger & Alice Lepelley & Ulrich Rupp & Susanne Klute & Victoria Hunszinger & Lennart Koepke & Veronika Merold & Blaise Didry-Barca & Fanny Wondany & Tim Bergner & Tatiana Moreau & , 2023. "ARF1 prevents aberrant type I interferon induction by regulating STING activation and recycling," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Martha Triantafilou & Joshi Ramanjulu & Lee M. Booty & Gisela Jimenez-Duran & Hakan Keles & Ken Saunders & Neysa Nevins & Emma Koppe & Louise K. Modis & G. Scott Pesiridis & John Bertin & Kathy Triant, 2022. "Human rhinovirus promotes STING trafficking to replication organelles to promote viral replication," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Xintao Tu & Ting-Ting Chu & Devon Jeltema & Kennady Abbott & Kun Yang & Cong Xing & Jie Han & Nicole Dobbs & Nan Yan, 2022. "Interruption of post-Golgi STING trafficking activates tonic interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Niranjana Natarajan & Jonathan Florentin & Ebin Johny & Hanxi Xiao & Scott Patrick O’Neil & Liqun Lei & Jixing Shen & Lee Ohayon & Aaron R. Johnson & Krithika Rao & Xiaoyun Li & Yanwu Zhao & Yingze Zh, 2024. "Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Stefanie Hiltbrunner & Lena Cords & Sabrina Kasser & Sandra N. Freiberger & Susanne Kreutzer & Nora C. Toussaint & Linda Grob & Isabelle Opitz & Michael Messerli & Martin Zoche & Alex Soltermann & Mar, 2023. "Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Jeffrey Patterson-Fortin & Heta Jadhav & Constantia Pantelidou & Tin Phan & Carter Grochala & Anita K. Mehta & Jennifer L. Guerriero & Gerburg M. Wulf & Brian M. Wolpin & Ben Z. Stanger & Andrew J. Ag, 2023. "RETRACTED ARTICLE: Polymerase θ inhibition activates the cGAS-STING pathway and cooperates with immune checkpoint blockade in models of BRCA-deficient cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Seethalakshmi Hariharan & Benjamin T. Whitfield & Christopher J. Pirozzi & Matthew S. Waitkus & Michael C. Brown & Michelle L. Bowie & David M. Irvin & Kristen Roso & Rebecca Fuller & Janell Hostettle, 2024. "Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    17. Yidan Wang & Ying Xu & Chee Wah Tan & Longliang Qiao & Wan Ni Chia & Hongyi Zhang & Qin Huang & Zhenqiang Deng & Ziwei Wang & Xi Wang & Xurui Shen & Canyu Liu & Rongjuan Pei & Yuanxiao Liu & Shuai Xue, 2022. "Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29946-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.