Figure 2.

Signaling through Mincle and MCL. (A) Mincle and MCL pair with the signaling adaptor molecule Fc receptor γ-chain (FcRγ). With Mincle this association is driven by the presence of a positively charged arginine in the transmembrane region whereas the corresponding residue is not present in MCL. Upon binding to DAMPs or fungal and bacterial PAMPs, phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs) of FcRγ recruits spleen tyrosine kinase (Syk) and induces signaling through the Card9–Bcl10–MALT1 complex. Transcription results in the formation of immunoregulatory cytokines and chemokines. (B) Heterodimers of MCL and Mincle have the capacity to sense trehalose dimycolate (TDM). In these complexes, Mincle recognizes the carbohydrate headgroup while MCL recognizes the lipid tail, and Mincle acts as a bridge to enable formation of a functional MCL–Mincle–FcRγ complex.