Human macrophage C‐type lectin forms a heteromeric receptor complex with Mincle but not Dectin‐2

Abstract

MCL, Mincle and Dectin‐2 are C‐type lectin receptors expressed by subsets of myeloid cells, and their genes cluster together in the APLEC/Dectin‐2 gene complex. We have previously shown that MCL and Mincle form a heterodimer in the rat, and others have shown that MCL and Dectin‐2 form a heterodimer in the mouse. In the rat, Dectin‐2 is a pseudogene, but here, we examine the association of the three receptors in human. In co‐transfection experiments analyzed with flow cytometry and immunoprecipitation, we here show that human MCL and Mincle form a disulphide‐linked heterodimer that associates with the signalling adaptor molecule FcεRIγ, in accordance with our previous findings in the rat. In contrast to previous findings in the rat, data in this paper indicate a direct association of MCL with FcεRIγ, as previously shown for mouse MCL. We were unable to demonstrate the formation of a heterodimer between human MCL and Dectin‐2. Thus, despite similarities, there may be important differences in the conformation of these receptors between rat, mouse and human, and this may have functional consequences.

Card9 and MyD88 differentially regulate Th17 immunity to the commensal yeastMalasseziain the murine skin

“…1A). Considering that Dectin-3 primarily acts in association with other CLRs [23], [24], [25] we focused on Mincle, Dectin-1 and Dectin-2 [19][20][21] . To test the binding capacity of these receptors to Malassezia, we made use of soluble murine CLR-Fc constructs [26], [27], [28].…”

Dectin‐3‐targeted antifungal liposomes efficiently bind and kill diverse fungal pathogens

“…The implication is that physically connected heteromeric CRDs of the two CTLs are formed and have novel properties of ligand recognition. By contrast, when co‐transfected into embryonic kidney 293 T cells, Dectin‐2 did not appear to form heteromeric complexes with Dectin‐3 (Blankson et al, 2022 ). Thus, it is possible that other factors are required for their linked behavior.…”

Secondary Sites of the C‐type Lectin‐Like Fold

“…[33][34][35] For other members of group II, such as macrophage inducible C-type lectin (mincle) and macrophage C-type lectin (MCL), heterodimerization via the stalk and an intermolecular disulfide bond impacts expression, endocytosis and signaling activity. [36,37] CTLs of group V display similar domain architecture and have been separated from group II based on phylogenetic analysis. [3] Their CTLD lacks Ca 2 + -coordination motifs, thus also canonical Ca 2 + -dependent carbohydrate binding activity.…”

“…For prominent examples of this group, such as DC‐SIGN, langerin, and macrophage galactose lectin (MGL), an elongated stalk domain enables homooligomerization via coiled‐coil interactions and facilitates multivalent recognition of glycosylated ligands [33–35] . For other members of group II, such as macrophage inducible C‐type lectin (mincle) and macrophage C‐type lectin (MCL), heterodimerization via the stalk and an intermolecular disulfide bond impacts expression, endocytosis and signaling activity [36,37] . CTLs of group V display similar domain architecture and have been separated from group II based on phylogenetic analysis [3] .…”