Fig. 1.

Scheme illustrating the structure, localization and signaling pathways affected by the CX3CL1–CX3CR1 axis. CX3CL1, produced mostly by neurons, is a membrane-bound molecule with a chemokine domain, mucin-like stalk, transmembrane region and cytoplasmic tail. Cleavage of CX3CL1 is mediated under physiological or pathological conditions by ADAM10 or ADAM17, MMP-2, MMP-3 and cathepsin S, respectively. Binding CX3CL1 to CX3CR1, which is a seven-transmembrane domain G_i protein-coupled receptor expressed primarily on microglia, results in an intracellular transmission engaging multiple signaling pathways. TM transmembrane domain, EL extracellular loop, IL intracellular loop