Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 132, Issue 5, Pages 1443-1451Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2011.478
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Funding
- AvH Foundation [DEU/1128670]
- Deutsche Forschungsgemeinschaft [BO 3643/2-1, PE 1478/5-1, SFB894, NI671/3-1]
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UV radiation of the skin triggers keratinocytes to secrete endothelin-1 (ET-1) that binds to endothelin receptors on neighboring melanocytes. Melanocytes respond with a prolonged increase in intracellular Ca2+ concentration ([Ca2+](i)), which is necessary for proliferation and melanogenesis. A major fraction of the Ca2+ signal is caused by entry through Ca2+-permeable channels of unknown identity in the plasma membrane. ORAI Ca2+ channels are molecular determinants of Ca2+ release-activated Ca2+ (CRAC) channels and are expressed in many tissues. Here, we show that ORAI1-3 and their activating partners stromal interaction molecules 1 and 2 (STIM1 and STIM2) are expressed in human melanocytes. Although ORAI1 is the predominant ORAI isoform, STIM2 mRNA expression exceeds STIM1. Inhibition of ORAI1 by 2-aminoethoxydiphenyl borate (2-APB) or downregulation of ORAI1 by small interfering RNA (siRNA) reduced Ca2+ entry and CRAC current amplitudes in activated melanocytes. In addition, suppression of ORAI1 caused reduction in the ET-1-induced cellular viability, melanin synthesis, and tyrosinase activity. Our results imply a role for ORAI1 channels in skin pigmentation and their potential involvement in UV-induced stress responses of the human skin.
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