Intracellular Vesicular Trafficking of Tyrosinase Gene Family Protein in Eu‐ and Pheomelanosome Biogenesis

Abstract

The intracellular vesicular trafficking in the melanosome biogenesis (melanogenesis) is reviewed with the incorporation of our own experimental findings. The melanosome biogenesis involves four stages of melanosome maturation, which reflect the transport of structural and enzymatic proteins from Golgi (trans-Golgi network: TGN) to the melanosomal compartment and their organization therein. The major melanosomal proteins include tyrosinase gene family protein (tyrosinase and tyrosinase-related protein; TRP), lysosome-associated membrane protein (Lamp) and gp100 (pmel 17). They are glycosylated in the endoplasmic reticulum, and transported by vesicles from the TGN to the melanosomal compartment. During the formation of transport vesicles, they assemble on the cytoplasmic face of the TGN to select cargo by interacting 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 late endosomes) and then to stage II melanosomes. A number of small guanosine triphosphate-binding proteins, including rab 7, appear to be involved in this vesicular transport. Phosphatidyl inositol 3 kinase also regulates this membrane trafficking of melanosomal glycoprotein. Eumelanogenesis is controlled by melanocyte-stimulating hormone, and all three tyrosinase gene family proteins are transported from the TGN to stage II melanosomes that are elliposoidal and contain the structural matrix of filaments/lamellae. In contrast, pheomelanogenesis is primarily regulated by agouti signal protein, and only tyrosinase is transported from stage I melanosomes to stage II melanosomes that are spherical and related to lysosomes. Because of the absence of TRP-1 and TRP-2 in pheomelanogenesis, it may be suggested that tyrosinase 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.

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

“…Lysosomal enzymes are ultimately delivered to lysosomes either by maturation of the prelysosomes or vesicular transport to or fusion with pre-existing lysosomes (Mullock et al, 1998;Karlsson et al, 1998). It has been recently indicated that membrane proteins are targeted to lysosomes and melanosomes using the same or similar targeting motif, i.e., tyrosine-or di-leucine-based motifs, respectively (Vijayasaradhi et al, 1995;Jimbow et al, 2000a). Calvo et al (1999) characterized sorting determinants of tyrosinase, and found, using HeLa cells, that the cytoplasmic domain of tyrosinase was necessary not only for internalization to but also for its steady-state localization in late endosomes and lysosomes.…”

“…Tyrosinase family protein is glycosylated and assembled in the ER with the help of a molecular chaperone, calnexin (Toyofuku et al, 1999). It is then transported from the trans-Golgi network (TGN) to melanosomes through intracellular transport vesicles (Jimbow et al, 2000a). Our recent studies as well as those of others indicate that a number of intracellular transporters are involved in this melanogenesis cascade, including adaptor protein (AP3), a number of small guanosine triphosphate-binding proteins, including rab7, and phosphoinositide 3 kinase (Jimbow et al, 2000b).…”

Mechanisms of pigmentation loss in subterranean fishes

“…In contrast, in those melanosomes in which there is synthesis of pheomelanin only material with grain aspect is observed in all the maturation phases. (Jimbow et al, 2000).…”

Estudo sistemático da ação melanogênica do ext rato de Brosimum gaudichaudii Trécul

“…As unidades epidérmico-melânicas são formadas pela associação de melanócitos e queratinócitos na proporção de 1:30. O número de melanócitos/mm 2 é em torno de dois mil nas áreas mais expostas ao UV e cerca de mil no restante do corpo (Jimbow et al, 2000). Os diferentes tons de pele e pelos não dependem do número de melanócitos, mas sim, do grau da atividade de síntese da melanina e da proporção entre eumelanina e feumelanina sintetizada (Jimbow et al, 2000;Jones et al, 2002).…”

“…Os diferentes tons de pele e pelos não dependem do número de melanócitos, mas sim, do grau da atividade de síntese da melanina e da proporção entre eumelanina e feumelanina sintetizada (Jimbow et al, 2000;Jones et al, 2002). Figura 6: Disposição dos melanócitos na epiderme A síntese da melanina é restrita ao melanossomas contidos nos citoplasmas dos melanócitos (Miranda e Botti, 1983;Jimbow et al, 2000;Jimbow K, 2000), e é iniciada pela hidroxilação da tirosina pela ação da tirosina hidroxilase, formando a DOPA, sendo oxidada pela DOPAquinase formando a DOPAquinona (PHILIPPSEN, 2006;KORMOS et al, 2010). A DOPAquinona é um intermediário altamente reativo, que na ausência de compostos tióis sofre ciclização, levando à produção de eumelanina, de cor preta ou marrom.…”