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

2017 Fiscal Year Final Research Report

• Project/Area Number: 26860201
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Fukushima 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
• Keywords: コアフコース / TLR4 / CD14 / 細胞内輸送 / インターフェロン-β

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.

Free Research Field

糖鎖生物学