Oral communication, CS24 / C115

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Characterization of the bioactive motif of neuregulin-1, a fibroblast-derived paracrine factor that regulates constitutive color and melanocyte function in human skin

Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We previously demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling (J Cell Biol, 2004). Similarly, fibroblasts in the dermis also play a role in regulating constitutive skin color of individuals ranging from very light to very dark via secretion of neuroregulin 1 (NRG-1) (J Cell Sci, 2010). Both of those factors cause their effects by interacting with specific receptors expressed on the surface of melanocytes, and the signaling pathways affected then regulate melanocyte differentiation. We have now begun mapping the bioactive domain in NRG-1 that is involved in regulating pigmentation and are identifying the minimal bioactive motif within the EGF domain of NRG-1 that is sufficient to increase the pigmentation of normal human melanocytes. We show that overlapping 8-mers within the EFG domain are able to mimic the stimulatory activity of the complete protein, and our goal is to identify even smaller peptides that are bioactive. This information will be useful for the future in vivo application of NRG-1 to regulate human skin pigmentation.

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