Slit proteins were identified as secreted ligands that mediate neuronal repulsion through interaction with members of the Robo family of single transmembrane receptors. Now Wu et al. have shown that Slit2 and Slit3 and the Robo1 receptor are expressed in several non-neuronal tissues. In leukocyte migration assays, Slit2 inhibited migration stimulated by the chemokine SDF-1a and by the bacterial peptide N-formyl-Met-Leu-Phe (fMLP). This was not due to simple repulsion but represented an inhibition of the attraction signaling mechanism, so that Slit2 was able to inhibit migration when applied to either the chamber containing the cells or the target chamber. Inhibition of SDF-1a-stimulated migration by Slit2 could be reconstituted in human embryonic kidney cells after cotransfection of the chemokine receptor CXCR4, a G protein-coupled receptor (GPCR) and Robo1, which suggests that the two receptors may interact functionally. Thus, the molecular mechanisms of guidance pathways across multiple systems appear to be conserved. Slit2 and Robo1 may represent new avenues of exploration for controlling leukocyte-mediated inflammatory processes. — NG
Nature410, 984 (2001).