UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes.
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. The molecular mechanisms used by melanocytes to detect and respond to long-wavelength UVR (UVA) are not well understood. We recently identified a UVA phototransduction pathway in melanocytes that is mediated by G protein-coupled receptors and leads to rapid calcium mobilization. Here we report that in human epidermal melanocytes physiological doses of UVR activate a retinal-dependent current mediated by transient receptor potential A1 (TRPA1) ion channels. The TRPA1 photocurrent is UVA-specific and requires G protein and phospholipase C signaling, thus contributing to UVA-induced calcium responses to mediate downstream cellular effects and providing evidence for TRPA1 function in mammalian phototransduction. Remarkably, TRPA1 activation is required for the UVR-induced and retinal-dependent early increase in cellular melanin. Our results show that TRPA1 is essential for a unique extraocular phototransduction pathway in human melanocytes that is activated by physiological doses of UVR and results in early melanin synthesis.
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
Nicholas W
NW
Bellono
Laura G
LG
Kammel
Anita L
AL
Zimmerman
Elena
E
Oancea
D000818:Animals; D016466:CHO Cells; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D020013:Calcium Signaling / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D055537:Light Signal Transduction / Q000502:physiology* / Q000528:radiation effects*; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D015220:Calcium Channels; D008543:Melanins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D019204:GTP-Binding Proteins