| First Author | Takano T | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 41 | Pages | 16933-16941 |
| PubMed ID | 28848046 | Mgi Jnum | J:247197 |
| Mgi Id | MGI:5917098 | Doi | 10.1074/jbc.M117.800847 |
| Citation | Takano T, et al. (2017) Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity. J Biol Chem 292(41):16933-16941 |
| abstractText | 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 beta-glucan. We report here that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. Low-valency beta-glucan components within fucan appeared to be responsible for this activation, as the ligand activity was eliminated by beta-glucanase treatment. The low-valency beta-glucan laminarin also acted as an agonist for human Dectin-1 but not for mouse Dectin-1, whereas the high-valency beta-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 beta-glucan. Rather, we found that its intracellular domain renders human Dectin-1 reactive to low-valency beta-glucan 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 beta-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 beta-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. |
