Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ.
Upon receptor activation, the myeloid C-type lectin receptor Mincle signals via the Syk-CARD9-Bcl10-MALT1 pathway. It does so by recruiting the ITAM-bearing FcεRI-γ. The related receptor macrophage C-type Lectin (MCL) has also been shown to be associated with Syk and to be dependent upon this signaling axis. We have previously shown that MCL co-precipitates with FcεRI-γ, but were unable to show a direct association, suggesting that MCL associates with FcεRI-γ via another molecule. Here, we have used rat primary cells and cell lines to investigate this missing link. A combination of flow cytometric and biochemical analysis showed that Mincle and MCL form heteromers on the cell surface. Furthermore, association with MCL and FcεRI-γ increased Mincle expression and enhanced phagocytosis of Ab-coated beads. The results presented in this paper suggest that the Mincle/MCL/FcεRI-γ complex is the functionally optimal form for these C-type lectin receptors on the surface of myeloid cells.
Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Ana
A
Lobato-Pascual
Per Christian
PC
Saether
Sigbjørn
S
Fossum
Erik
E
Dissen
Michael R
MR
Daws
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D055503:Protein Multimerization / Q000276:immunology*; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism
D037181:Lectins, C-Type; D046912:Multiprotein Complexes; D017455:Receptors, IgE
C‐type lectin; Macrophage C‐type Lectin (MCL); Mincle; Myeloid cells; Signaling adaptor