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Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to Melanosomes

2005; American Society for Cell Biology; Volume: 16; Issue: 11 Linguagem: Inglês

10.1091/mbc.e05-07-0626

1939-4586

Alexander C. Theos, Danièle Tenza, José A. Martina, Ilse Hurbain, Andrew A. Peden, Elena V. Sviderskaya, Abigail Stewart, Margaret S. Robinson, Dorothy C. Bennett, Daniel F. Cutler, Juan S. Bonifacino, Michael S. Marks, Graça Raposo,

RNA regulation and disease

Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies.