Fig. 3.

Keratinocyte-melanocyte cross-talk: proposed barrier-initiated signals. Nerve growth factor (NGF) and interleukin 1α (IL-1α) signal many downstream pigmentary responses, but both also increase in response to stress to the barrier. Recently recognized keratinocyte signals (stem cell factor [SCF], FOXn1→FGF2 [fibroblast growth factor 2], and p53) could be activated not only by UV-B, but also by stress to the barrier from a decreased relative humidity, which could be “sensed” by the transient vanilloid receptor, type 4 (TRPV4). Stressor-induced ligands also increase the melanocortin receptor type 1 (MC1R), which upregulates eumelanin synthesis (tyrosinase, TYR), perhaps by increasing expression of ion/pH transporters that increase melanosome acidification, and/or the melanosome transporter, myosin VA. Transfer of large, single melanosome complexes from melanocyte dendrites (M) to keratinocytes (K) in the outer epidermis further acidifies the stratum corneum (SC). See text for additional abbreviations.