Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes |
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| Authors: | Theos Alexander C Tenza Danièle Martina José A Hurbain Ilse Peden Andrew A Sviderskaya Elena V Stewart Abigail Robinson Margaret S Bennett Dorothy C Cutler Daniel F Bonifacino Juan S Marks Michael S Raposo Graça |
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| Affiliation: | Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust, Cambridge CB2 2XY, United Kingdom. |
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| Abstract: | 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. |
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