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The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor

Author

Listed:
  • Sarah E. Ewald

    (University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA)

  • Bettina L. Lee

    (University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA)

  • Laura Lau

    (University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA)

  • Katherine E. Wickliffe

    (University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA)

  • Guo-Ping Shi

    (Brigham and Women’s Hospital, Harvard Medical School, NRB-7, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA)

  • Harold A. Chapman

    (and The Cardiovascular Research Institute, University of California, San Francisco, Box 0111, San Francisco, California 94143, USA)

  • Gregory M. Barton

    (University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA)

Abstract

Autoimmunity: TLR9 activation The role of the Toll-like receptors TLR9 and TLR7 in mediating autoimmune disease to self nucleic acid is now well appreciated, yet the mechanisms preventing rampant autoimmunity remain largely unknown. Here Ewald et al. define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. TLR9 activation is shown to require proteolytic cleavage in the endolysosome. This may be a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids.

Suggested Citation

  • Sarah E. Ewald & Bettina L. Lee & Laura Lau & Katherine E. Wickliffe & Guo-Ping Shi & Harold A. Chapman & Gregory M. Barton, 2008. "The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor," Nature, Nature, vol. 456(7222), pages 658-662, December.
    • Handle: RePEc:nat:nature:v:456:y:2008:i:7222:d:10.1038_nature07405
    DOI: 10.1038/nature07405
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    Cited by:

    1. Srujan Kumar Dondapati & Georg Pietruschka & Lena Thoring & Doreen A Wüstenhagen & Stefan Kubick, 2019. "Cell-free synthesis of human toll-like receptor 9 (TLR9): Optimization of synthesis conditions and functional analysis," PLOS ONE, Public Library of Science, vol. 14(4), pages 1-16, April.
    2. Hai Ni & Yinuo Wang & Kai Yao & Ling Wang & Jiancheng Huang & Yongfang Xiao & Hongyao Chen & Bo Liu & Cliff Y. Yang & Jijun Zhao, 2024. "Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Yoann Saucereau & Thomas H. Wilson & Matthew C. K. Tang & Martin C. Moncrieffe & Steven W. Hardwick & Dimitri Y. Chirgadze & Sandro G. Soares & Maria Jose Marcaida & Nicholas J. Gay & Monique Gangloff, 2022. "Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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