Figure 2.

TREM2 molecular signaling in microglia, initiating phagocytosis and microglial survival or modulating proinflammatory response, is not well characterized so only validated components are displayed. In vitro studies have suggested possible ligands for TREM2, which bind TREM2 to initiate signaling. TREM2 associates with DAP12, which is phosphorylated to activate signaling through recruitment of spleen tyrosine kinase (Syk). Syk activates the Ras/extracellular signal-regulated kinase (ERK)/protein kinase C (PKC) pathway to initiate phagocytosis. Microglial survival is initiated by the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway. TREM2 is thought to influence inflammatory response by inhibiting the c-Jun N-terminal kinase (JNK) pathway which can be activated when ligands like lipopolysaccharide (LPS) bind toll-like receptor-4 (TLR4), initiating the production of proinflammatory cytokines.