Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity

Tomotsugu Takano, Chihiro Motozono, Takashi Imai, Koh Hei Sonoda, Yoichi Nakanishi, Sho Yamasaki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

C-type lectin receptors (CLRs) comprise a large family of immunoreceptors that recognize polysaccharide ligands exposed on pathogen surfaces and are conserved among mammals. However, interspecies differences in their ligand spectrums are not fully understood. Dectin-1 is a well-characterized CLR that recognizes -glucan. We report here that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dec-tin-1. Low-valency -glucan components within fucan appeared to be responsible for this activation, as the ligand activity was eliminated by -glucanase treatment. The low-valency -glu-can laminarin also acted as an agonist for human Dectin-1 but not for mouse Dectin-1, whereas the high-valency -glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 does not determine its unique sensitivity to low-valency -glucan. Rather, we found that its intracellular domain renders human Dectin-1 reactive to low-valency -glu-can ligand. Substitution with two amino acids, Glu2 and Pro5, located in the human Dectin-1 intracellular domain was sufficient to confer sensitivity to low-valency -glucan in mouse Dectin-1. Conversely, the introduction of mouse-specific amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity to low-valency -glucan. Indeed, low-valency ligands induced a set of proinflammatory genes in human but not mouse dendritic cells. These results suggest that the intracellular domain, not ligand-binding domain, of Dectin-1 determines the species-specific ligand profile.

Original languageEnglish
Pages (from-to)16933-16941
Number of pages9
JournalJournal of Biological Chemistry
Volume292
Issue number41
DOIs
Publication statusPublished - Jan 1 2017

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Ligands
Glucans
C-Type Lectins
dectin 1
Seaweed
Amino Acids
Mutagenesis
Mammals
Tin
Pathogens
Dendritic Cells
Polysaccharides
Substitution reactions
Genes
Chemical activation
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity. / Takano, Tomotsugu; Motozono, Chihiro; Imai, Takashi; Sonoda, Koh Hei; Nakanishi, Yoichi; Yamasaki, Sho.

In: Journal of Biological Chemistry, Vol. 292, No. 41, 01.01.2017, p. 16933-16941.

Research output: Contribution to journalArticle

Takano, Tomotsugu ; Motozono, Chihiro ; Imai, Takashi ; Sonoda, Koh Hei ; Nakanishi, Yoichi ; Yamasaki, Sho. / Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 41. pp. 16933-16941.
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