title: Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes.
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.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust, Cambridge CB2 2XY, United Kingdom.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Theos
authors.forename: Danièle
authors.initials: D
authors.lastname: Tenza
authors.forename: José A
authors.initials: JA
authors.lastname: Martina
authors.forename: Ilse
authors.initials: I
authors.lastname: Hurbain
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Peden
authors.forename: Elena V
authors.initials: EV
authors.lastname: Sviderskaya
authors.forename: Abigail
authors.initials: A
authors.lastname: Stewart
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Robinson
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Cutler
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marks
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000502:physiology*; D033963:Adaptor Protein Complex 3 / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008544:Melanocytes / Q000378:metabolism / Q000648:ultrastructure; D020460:Melanosomes / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D033961:Adaptor Protein Complex 1; D033963:Adaptor Protein Complex 3; D021382:Protein Sorting Signals; D014442:Monophenol Monooxygenase