sAPP as a regulator of dendrite motility and melanin release in epidermal melanocytes and melanoma cells

Numerous factorsincludingultraviolet(UV)radiation and growth factors regulate the specific function of epidermal melanocytes. A recently discovered epidermal growth factor is sAPP, the soluble N-terminal ectodomain of the beta-amyloid precursor protein(APP). Using whole mount preparations of isolated human epidermis,we detected a small population of basal cells, which expressed exceptionally highlevelsofAPP.Thesecellswereidentifiedasmelanocytes,which,similar to keratinocytes and neuronal cells, expressed the three APP isoforms 695,751,and 770. They differed in their expression pattern from that of neuronal cells by expressing onlylowlevelsofAPP695.Melanocytesandmelanomacellsinvitroreleased,in addition to keratinocytes,large quantities of sAPP. Because of its growth factor function,we studied possible effects of sAPP on melanocytes. Recombinants APPstronglyincreasedlamellipodiaactivityatdendritictips,an effect that coincided with increased release of melanin particles. Our observations point to the possible use of APP as an immunocytochemical marker for melanocytes. They suggest that sAPP derived from keratinocytes and/or melanocytes belongs to a family of factors operating in the paracrine and/or autocrine regulation of melanocyte function.