Intracellular vesicular trafficking of tyrosinase gene family protein in Eu- and pheomelanosome biogenesis

The intracellular vesicular trafficking in the melanosome biogenesis (melan ogenesis) is reviewed with the incorporation of our own experimental findin gs. The melanosome biogenesis involves four stages of melanosome maturation . which reflect the transport of structural and enzymatic proteins from Gol gi (trans-Golgi network: TGN) to the melanosomal compartment and their orga nization therein. The major melanosomal proteins include tyrosinase gene fa mily protein (tyrosinase and tyrosinase-related protein; TRP), lysosome-ass ociated membrane protein (Lamp) and gp100 (pmel 17). They are glycosylated in the endoplasmic reticulum, and transported by vesicles from the TGN to t he melanosomal compartment. During the formation of transport vesicles, the y assemble on the cytoplasmic face of the TGN to select cargo by interactin g directly; or indirectly with coat proteins. Tyrosinase and TRP-1 possess the dileucine motifs at the cytoplasmic domain, to which adapter protein-3 binds to transport them from the TGN to stage I melanosomes (related to lat e endosomes) and then to stage II melanosomes, A number of small guanosine triphosphate-binding proteins, including rab 7, appear to be involved in th is vesicular transport. Phosphatidyl inositol 3 kinase also regulates this membrane trafficking of melanosomal glycoprotein. Eumelanogenesis is contro lled by melanocyte-stimulating hormone, and all three tyrosinase gene famil y proteins are transported from the TGN to stage II melanosomes that are el liposoidal and contain the structural matrix of filaments/lamellae. In cont rast, pheomelanogenesis is primarily regulated by agouti signal protein, an d only tyrosinase is transported from stage I melanosomes to stage II melan osomes that are spherical and related to lysosomes, Because of the absence of TRP-1 and TRP-2 in pheomelanogenesis, it may be suggested that tyrosinas e is involved in lysosomal degradation after forming dopaquinone, to which the cysteine present in the lysosomal granule binds to form cysteinyldopas that will then be auto-oxidized to become pheomelanin.