Ultraviolet Light Phototransduction Activates TRPA1 to Mediate Melanin Synthesis in Human Melanocytes

Abstract

Human skin is constantly exposed to solar ultraviolet radiation (UVR), the most prevalent environmental carcinogen. Humans have the unique ability among mammals to respond to UVR by increasing their skin pigmentation, a protective process driven by melanin synthesis in epidermal melanocytes. However, the mechanism used by melanocytes to detect and respond to UVR is not well understood. Here we report that transient receptor potential A1 (TRPA1) ion channels expressed in human melanocytes are activated by UVR and mediate early melanin synthesis. We show that in human epidermal melanocytes (HEMs) physiological doses of UVR activate a retinal-dependent current mediated by TRPA1. The UVR photocurrent density was reduced by TRPA1 antagonists and abolished in HEMs expressing TRPA1-targeted miRNA. The TRPA1 photocurrent is UVA specific and requires G protein signaling, providing the first evidence for TRPA1 function in mammalian phototransduction. In HEMs, TRPA1 activation contributes to UVR-induced calcium responses to mediate downstream cellular effects. Remarkably, the UVR-induced and retinal-dependent early increase in cellular melanin content was significantly reduced in HEMs treated with TRPA1 antagonists and abolished in HEMs expressing TRPA1-targeted miRNA, suggesting that TRPA1 is required for early melanin synthesis. Our results show that TRPA1 is essential for a novel extra-ocular phototransduction pathway in human melanocytes that is activated by physiological doses of UVR and results in early melanin synthesis.