CXCR7 mediates SDF1-induced melanocyte migration.

Melanoblasts are derived from the neural crest and migrate to the dermal/epidermal border of skin and hair bulges. Although melanoblast migration during embryogenesis has been well investigated, there are only a few reports regarding the migration of mature melanocytes. Here, we demonstrate that a chemokine, stromal-derived factor-1 (SDF1, also known as CXCL12), and one of its receptor CXCR7 regulate normal human epidermal melanocyte (NHEM) migration. We found that SDF1 induces the directional migration of NHEMs. Interestingly, although both CXCR4 and CXCR7 are expressed in NHEMs, blockade of CXCR4 using a CXCR4-specific neutralizing antibody did not exert any influence on the SDF1-induced migration of NHEMs, whereas blockade of CXCR7 using a CXCR7-specific neutralizing antibody did influence migration. Furthermore, SDF1-induced NHEMs migration exhibited the early hallmark events of CXCR7 signaling associated with MAP kinase activation. It is known that the phosphorylation of ERK through CXCR7 signaling is mediated by β-arrestins. The treatment of NHEMs with SDF1 resulted in the phosphorylation of ERK in a β-arrestin 2-dependent manner. These results suggest that melanocytes may have a unique mechanism of migration via SDF1/CXCR7 signaling that is different from that of other cell types.