Interaction of DAP12 and TREM2

Stable Identifier
R-HSA-210300
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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TREM2 (triggering receptor expressed on myeloid cells 2 protein) is expressed on the cell membrane of a subset of myeloid cells - namely, immature dendritic cells, osteoclasts, tissue macrophages, and microglia. Like TREM1 the ligand for TREM2 is unknown. TREM2 signals through DAP12, leading to an increase in intracellular calcium and phosphorylation of ERK1/2 (Sharif & Knapp. 2008). It recognises anionic lipopolysacharides in the cell wall of bacteria and triggers the phagocytic uptake of bacteria and the release of reactive oxygen species (Neumann & Daly 2013). TREM2 on immature dendritic cells triggers upregulation of molecules involved in T cell co-stimulation such as CD86, CD40 and MHC class II, as well as up-regulation of the chemokine receptor CCR7 (Bouchon et al. 2001). In macrophages TREM2 is a negative regulator of inflammatory responses (Hamerman et al. 2006, Turnbull et al. 2006). From genome wide association studies, a TREM2 variant (encoding a substitution of arginine by histidine at residue 47 [R47H]) has been reported to be implicated in late-onset Alzheumer's disease (Neumann & Daly 2013).

Literature References
PubMed ID Title Journal Year
11602640 A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells

Bouchon, A, Hernández-Munain, C, Cella, M, Colonna, M

J. Exp. Med. 2001
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