PMID- 28973141
OWN - NLM
STAT- MEDLINE
DCOM- 20180530
LR  - 20180730
IS  - 1460-2423 (Electronic)
IS  - 0959-6658 (Linking)
VI  - 27
IP  - 11
DP  - 2017 Nov 1
TI  - Core fucose is critical for CD14-dependent Toll-like receptor 4 signaling.
PG  - 1006-1015
LID - 10.1093/glycob/cwx075 [doi]
AB  - Core fucosylation, a posttranslational modification of N-glycans, modifies 
      several growth factor receptors and impacts on their ligand binding affinity. 
      Core-fucose-deficient mice generated by ablating the alpha1,6 fucosyltransferase 
      enzyme, Fut8, exhibit severe pulmonary emphysema, partly due to impaired 
      macrophage function, similar to aged Toll-like receptor 4 (Tlr4)-deficient mice. 
      We therefore suspect that a lack of core fucose affects the 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-beta (IFN-beta) compared with wild-type MEFs. 
      Lectin blot analysis of the TLR4 signaling complex revealed that core 
      fucosylation was specifically found on CD14. Even though similar levels of 
      TLR4/myeloid differentiation factor 2 (MD2) activation and dimerization were 
      observed in Fut8-deficient cells after lipopolysaccharide stimulation, 
      internalization of TLR4 and CD14 was significantly impaired. Given that 
      internalized TLR4/MD2 induces IFN-beta production, impaired IFN-beta 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.
CI  - (c) The Author 2017. Published by Oxford University Press. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Iijima, Junko
AU  - Iijima J
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Kobayashi, Satoshi
AU  - Kobayashi S
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Kitazume, Shinobu
AU  - Kitazume S
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Kizuka, Yasuhiko
AU  - Kizuka Y
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Fujinawa, Reiko
AU  - Fujinawa R
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Korekane, Hiroaki
AU  - Korekane H
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Shibata, Takuma
AU  - Shibata T
AD  - Division of Innate Immunity, Institute of Medical Science, The University of 
      Tokyo, Tokyo 108-8639, Japan.
FAU - Saitoh, Shin-Ichiroh
AU  - Saitoh SI
AD  - Division of Innate Immunity, Institute of Medical Science, The University of 
      Tokyo, Tokyo 108-8639, Japan.
FAU - Akashi-Takamura, Sachiko
AU  - Akashi-Takamura S
AD  - Department of Microbiology and Immunology, Aichi Medical University School of 
      Medicine, Aichi 480-1195, Japan.
FAU - Miyake, Kensuke
AU  - Miyake K
AD  - Division of Innate Immunity, Institute of Medical Science, The University of 
      Tokyo, Tokyo 108-8639, Japan.
FAU - Miyoshi, Eiji
AU  - Miyoshi E
AD  - Department of Molecular Biochemistry and Clinical Investigation, Osaka University 
      Graduate School of Medicine, Osaka 565-0871, Japan.
FAU - Taniguchi, Naoyuki
AU  - Taniguchi N
AD  - Disease Glycomics Team, RIKEN-Max Planck Joint Research Center, Global Research 
      Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Glycobiology
JT  - Glycobiology
JID - 9104124
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Toll-Like Receptor 4)
RN  - 28RYY2IV3F (Fucose)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 2.4.1.- (Fucosyltransferases)
RN  - EC 2.4.1.68 (Glycoprotein 6-alpha-L-fucosyltransferase)
SB  - IM
MH  - Animals
MH  - Fucose/*metabolism
MH  - Fucosyltransferases/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Interferon-beta/genetics/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Lipopolysaccharide Receptors/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Protein Processing, Post-Translational
MH  - *Signal Transduction
MH  - Toll-Like Receptor 4/*metabolism
OTO - NOTNLM
OT  - CD14
OT  - IFN-beta
OT  - TLR4
OT  - core fucose
OT  - endocytosis
EDAT- 2017/10/04 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/10/04 06:00
PHST- 2016/09/29 00:00 [received]
PHST- 2017/08/21 00:00 [accepted]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/10/04 06:00 [entrez]
AID - 4096881 [pii]
AID - 10.1093/glycob/cwx075 [doi]
PST - ppublish
SO  - Glycobiology. 2017 Nov 1;27(11):1006-1015. doi: 10.1093/glycob/cwx075.