A Melanosome-associated Monoclonal Antibody J1 Recognizes Luminal Membrane of Prelysosomes Common to Biogenesis of Melanosomes and Lysosomes.

Abstract

ABSTRACT. Melanogenesis cascade may be directly or indirectly linked to the dynamics of endosome-lysosome biogenesis. This study aims to identify how and to what extent the endosome-lysosome system is involved in melanosome biogenesis, by utilizing a novel melanogenesis marker, J1, which we identified in the process of developing monoclonal antibodies (MoAbs) against human melanosomes. The antigenic epitope of MoAb J1 was expressed by all of the melanotic and nonmelanotic cells examined. It was expressed primarily by granular structures located in regions proximal to the Golgi complex. Most of MoAb J1 positive granules were co-stained with melanogenic markers, tyrosinase or tyrosinase-related protein (TRP-1). The epitope of MoAb J1 was also coexpressed by most, but not all, of LGP85 (a lysosomal marker) positive granules in both melanoma and non-melanoma cells, indicating that MoAb J1 recognizes a subset of lysosomal vesicles. MoAb J1 did not, however, react with vesicles with late/early (syntaxin 8/ EEA1) endosomal markers. Further examination using fluorophore-labeled pepstatin, a marker of lysosomal luminal content, confirmed that MoAb J1 specifically recognizes the luminal surface of lysosomes. These results indicate that MoAb J1 possesses an antigen epitope that is expressed in the luminal component of prelysosomal granules which are involved in the biogenesis cascade common to both melanosomes and lysosomes. We suggest that tyrosinase family protein, tyrosinase and TRP-1 are transported to melanosomes from TGN via these prelysosomal granules after being transiently transported to late endosomes.

Delta-Tocotrienol Causes Decrease of Melanin Content in Mouse Melanoma Cells

“…Melanosome biogenesis involves four stages of maturation with distinct morphological and biochemical characteristics that reflect the biogenesis process of structural and enzymatic proteins (tyrosinase family proteins), which is followed by structural organization and melanin deposition. 16) In general, it is thought that the antioxidant properties of tocotrienol decrease melanin levels by inhibiting oxidative enzymatic reactions, including tyrosinase or other enzymes in melanosomes. Therefore, tocotrienol may be an effective component in whitening and/or lightening cosmetics.…”