Molecular biology of the target signal for melanogenesis associated genes and vitiligo pathogenesis.

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This project has studied the biogenesis of melanosomes and function of melanin pigmentation in man for better understanding of the mechanism of leukoderma (e.g., vitiligo). Specifically we have utilized various molecular biology techniques including cDNA transfection of human tyrosinase and tyrosinase-related protein (TRP-1). We have characterized (1) correct assembly and folding of tyrosinase-gene family proteins with the help of calnexin, (2) target signals of tyrosinase-gene family proteins from TGN to melanosomes, (3) functional interactionbetween tyrosinase and lysosome-associated membrane protein in melanosome biogenesis, (4) mechanism of abnormal melanin synthesis in vitiligo melanocytes and (5) chemical modification of melanin precursor and development of depigmentation. The obtained results will be useful not only for better understanding of vitiligo pathogenesis but also for development of new selective melanocytotoxic agents