Jimbow K, Park J S, Kato F, Hirosaki K, Toyofuku K, Hua C, Yamashita T
Department of Dermatology, School of Medicine, Sapporo Medical University, Japan.
Pigment Cell Res. 2000 Aug;13(4):222-9. doi: 10.1034/j.1600-0749.2000.130403.x.
Assembly, target-signaling and transport of tyrosinase gene family proteins at the initial stage of melanosome biogenesis are reviewed based on our own discoveries. Melanosome biogenesis involves four stages of maturation with distinct morphological and biochemical characteristics that reflect distinct processes of the biosynthesis of structural and enzymatic proteins, subsequent structural organization and melanin deposition occurring in these particular cellular compartments. The melanosomes share many common biological properties with the lysosomes. The stage I melanosomes appear to be linked to the late endosomes. Most of melanosomal proteins are glycoproteins that should be folded or assembled correctly in the ER through interaction with calnexin, a chaperone associated with melanogenesis. These melanosomal glycoproteins are then accumulated in the trans Golgi network (TGN) and transported to the melanosomal compartment. During the formation of transport vesicles, coat proteins assemble on the cytoplasmic face of TGN to select their cargos by interacting directly or indirectly with melanosomal glycoproteins to be transported. Adapter protein-3 (AP-3) is important for intracellular transport of tyrosinase gene family proteins from TGN to melanosomes. Tyrosinase gene family proteins possess a di-leucine motif in their cytoplasmic tail, to which AP-3 appears to bind. Thus, the initial cascade of melanosome biogenesis is regulated by several factors including: 1) glycosylation of tyrosinase gene family proteins and their correct folding and assembly within ER and Golgi, and 2) supply of specific signals necessary for intracellular transport of these glycoproteins by vesicles from Golgi to melanosomes.
基于我们自己的发现，对黑素小体生物合成初始阶段酪氨酸酶基因家族蛋白的组装、靶向信号传导和运输进行了综述。黑素小体生物合成包括四个成熟阶段，具有不同的形态和生化特征，反映了结构和酶蛋白生物合成、随后的结构组织以及在这些特定细胞区室中发生的黑色素沉积的不同过程。黑素小体与溶酶体具有许多共同的生物学特性。I期黑素小体似乎与晚期内体相连。大多数黑素小体蛋白是糖蛋白，它们应通过与钙连蛋白（一种与黑色素生成相关的伴侣蛋白）相互作用，在内质网中正确折叠或组装。然后这些黑素小体糖蛋白在反式高尔基体网络（TGN）中积累，并运输到黑素小体区室。在运输小泡形成过程中，包被蛋白在TGN的细胞质面上组装，通过直接或间接与要运输的黑素小体糖蛋白相互作用来选择其货物。衔接蛋白3（AP-3）对于酪氨酸酶基因家族蛋白从TGN到黑素小体的细胞内运输很重要。酪氨酸酶基因家族蛋白在其细胞质尾部具有一个双亮氨酸基序，AP-3似乎与之结合。因此，黑素小体生物合成的初始级联反应受多种因素调节，包括：1）酪氨酸酶基因家族蛋白的糖基化及其在内质网和高尔基体中的正确折叠和组装，以及2）这些糖蛋白通过从高尔基体到黑素小体的小泡进行细胞内运输所需的特定信号的供应。
