Fig. 2

Key cell surface receptors in microglia that utilize PI3K-AKT signaling. CSF-1 or IL-34 binds to CSF-1R on microglia, triggering its dimerization, autophosphorylation and recruitment of PI3K. Endotoxin (LPS) binds to the TLR4 complex comprised of CD14 and MD-2, causing it to dimerize and induce recruitment of the adaptor MyD88, leading to its phosphorylation and the promotion of PI3K signaling. Neurotoxic plaques or other agonists bind to TREM2 and the co-associated membrane-bound adaptor protein DAP12 becomes phosphorylated on tyrosine-containing activation motifs (ITAMs), resulting in PI3K recruitment and activation. CX3CL1 binds to CX3CR1 and triggers the activation of heterotrimeric G proteins that transduce an intracellular signal via PI3K