CX3CL1, also named neurotactin, is a novel chemokine identified through bioinformatics. CX3CL1 has a unique C-X3-C cysteine motif near the amino-terminus and is the first member of a fourth branch of the chemokine superfamily. Unlike other known chemokines, CX3CL1 is a type 1 membrane protein containing a chemokine domain tethered on a long mucin-like stalk. The extracellular domain of human CX3CL1 can be released, possibly by proteolysis at the dibasic cleavage site proximal to the
membrane, to generate soluble CX3CL1. CX3CL1 mRNA has been detected in various tissues including the brain and heart. The expression of CX3CL1 was also reported to be up-regulated in endothelial cells and microglia by inflammatory signals. Membrane-bound CX3CL1 has been shown to promote adhesion of leukocytes. The soluble chemokine domain of human CX3CL1 was reported to be chemotactic for T cells and monocytes while the soluble chemokine domain of mouse CX3CL1 was reported to
chemoattract neutrophils and T-lymphocytes but not monocytes. The gene for human CX3CL1 has been mapped to chromosome 16q.