Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12.

DNAX-activating protein of 12kDa (DAP12) is a member of type I transmembrane adapter proteins containing immunoreceptor tyrosine-based activation motifs (ITAMs). In humans DAP12 gene is located on chromosome 19q13.1. DAP12 forms a molecular complex with triggering receptor expressed on myeloid cells two (TREM-2). TREM-2 ligation leads to the activation of Src family kinases, phosphorylation of tyrosine residues in the ITAM of DAP12, recruitment of the Syk and ZAP70 tyrosine kinases and initiation of an intracellular signaling cascade. Depending on the cell type, DAP12/TREM-2 activation plays an important role in activation and differentiation of osteoclasts, phagocytosis of bacteria, brain and bone homeostasis and inhibition of the toll-like receptor (TLR) signaling in macrophages and dendritic cells. A proper understanding of the function of this complex receptor has been restrained because of the elusive nature of TREM-2 ligands. Here we review the structure, biological functions and signaling pathways of DAP12 and its associated receptor TREM-2.