Contribution of N-linked oligosaccharides to the expression and functions of beta-glucan receptor, Dectin-1.
Dectin-1 is a C-type lectin receptor that recognizes fungal beta-glucan, and mediates the production of reactive oxygen species and inflammatory cytokines. Thus Dectin-1 is thought to be essential for anti-fungal immune responses. Murine Dectin-1 mRNA is alternatively spliced and generates two isoforms (isoform A and B). Human Dectin-1 mRNA is also alternatively spliced and its functional isoforms (isoform A and B) are structurally similar to each of the mouse isoforms. One of the major differences among the four murine and human isoforms is the position and number of N-linked glycosylation motifs. But the significance of the glycosylation to the recognition of beta-glucan is not known. In this paper, using various glycosylation consensus sequence mutants, we demonstrated that the N-linked glycosylation of Dectin-1 affects the cell surface expression of the molecule. The expression levels on the cell surface influence the ligand-binding and the collaboration with TLR2 in the activation of NF-kappaB. These results suggest that N-linked glycosylation on Dectin-1 is essential for the recognition of fungal beta-glucan and subsequent activation of NF-kappaB.
Kato
Yuya
Y
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Adachi
Yoshiyuki
Y
Ohno
Naohito
N
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000099181:Dectin-1
D037181:Lectins, C-Type; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D009844:Oligosaccharides; D012333:RNA, Messenger; D000099181:Dectin-1