Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ

Eur J Immunol. 2013 Dec;43(12):3167-74. doi: 10.1002/eji.201343752. Epub 2013 Aug 26.

Abstract

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.

Keywords: C‐type lectin; Macrophage C‐type Lectin (MCL); Mincle; Myeloid cells; Signaling adaptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation / immunology
  • Humans
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / metabolism*
  • Multiprotein Complexes / immunology*
  • Multiprotein Complexes / metabolism
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology*
  • Phagocytosis / immunology
  • Protein Multimerization / immunology*
  • Rats
  • Receptors, IgE / immunology*
  • Receptors, IgE / metabolism

Substances

  • Lectins, C-Type
  • Multiprotein Complexes
  • Receptors, IgE