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Core fucose is critical for CD14-dependent Toll-like receptor 4 signaling.

Research Project

Project/Area Number 26860201
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionFukushima Medical University (2015-2017)
The Institute of Physical and Chemical Research (2014)

Principal Investigator

IIJIMA Junko  福島県立医科大学, 医学部, 助教 (10559636)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsコアフコース / TLR4 / CD14 / 細胞内輸送 / インターフェロン-β / endocytosis(細胞内への取り込み) / IFN-β / core fucose / endocytosis / 糖鎖 / 糖鎖生物学
Outline of Final Research Achievements

Core fucosylation, a posttranslational modification of N-glycans, modifies several growth factor receptors and impacts on their ligand binding affinity. We suspect that a lack of core fucose affects the Toll-like receptor 4 (Tlr4)-dependent signaling pathway.
Indeed, upon lipopolysaccharide stimulation, Fut8-deficient mouse embryonic fibroblasts (MEFs) produced similar levels of interleukin-6 but markedly reduced levels of interferon-β (IFN-β) compared with wild-type MEFs. Lectin blot analysis of the TLR4 signaling complex revealed that core fucosylation was specifically found on CD14. After lipopolysaccharide stimulation, internalization of TLR4 and CD14 was significantly impaired.
Given that internalized TLR4/ myeloid differentiation factor 2 (MD2) induces IFN-β production, impaired IFN-β production in Fut8-deficient cells is ascribed to impaired TLR4/MD2 internalization. These data show for the first time that glycosylation critically regulates TLR4 signaling.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report

Research Products

(4 results)

All 2017 2015 Other

All Journal Article Presentation Remarks

  • [Journal Article] Core fucose is critical for CD14-dependent Toll-like receptor 4 signaling.2017

    • Author(s)
      4.Iijima J, Kobayashi S, Kitazume S*, Kizuka Y, Fujinawa R, Korekane H, Shibata T, Saitoh S, Akashi-Takamura S, Miyake K, Miyoshi E, and Taniguch N
    • Journal Title

      Glycobiology

      Volume: 2017 Pages: 1006-1015

    • DOI
      10.1093/glycob/cwx075
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Toll様受容体4複合体を介した自然免疫の機能におけるコアフコースの意義2015

    • Author(s)
      飯島順子
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Toll様受容体4複合体を介した自然免疫の機能におけるコアフコースの意義2015

    • Author(s)
      飯島順子
    • Organizer
      Glyco TOKYO2015
    • Place of Presentation
      慶応義塾大学 矢上キャンパス
    • Year and Date
      2015-10-24
    • Related Report
      2015 Research-status Report
  • [Remarks] 病原体センサーの機能を変える糖鎖を発見 -コアフコースが自然免疫におけるシグナル伝達経路に必須-

    • URL
      http://www.riken.jp/pr/press/2017/20170915_1/
    • Related Report
      2017 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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