| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Diacylglycerol increases the melanin content of human melanocytes in vitro and increases the pigmentation of skin in vivo, but the mechanisms underlying those effects remain unknown. We characterized the role of diacylglycerol kinase (DGK) in the regulation of pigmentation. We examined the effect of DGK inhibitors on the modulation of melanogenesis in normal human epidermal melanocytes. Electron microscopy showed that the number of fibrillar and mature melanosomes was significantly reduced after treatment with DGK inhibitors. We therefore focused on the processing of PMEL17, a melanosomal glycoprotein that forms a fibrillar matrix on which melanin gets deposited. Recently, BACE2 was found to cleave PMEL17. We found that DGK inhibitors exerted effects on the processing of C-terminal and N-terminal fragments of PMEL17, and DGK affected PMEL17 processing in a BACE2-dependent mechanism. Furthermore, we identified downstream target of DGK signaling for melanogenesis.
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