Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes.
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.
Theos
Alexander C
AC
Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust, Cambridge CB2 2XY, United Kingdom.
Tenza
Danièle
D
Martina
José A
JA
Hurbain
Ilse
I
Peden
Andrew A
AA
Sviderskaya
Elena V
EV
Stewart
Abigail
A
Robinson
Margaret S
MS
Bennett
Dorothy C
DC
Cutler
Daniel F
DF
Bonifacino
Juan S
JS
Marks
Michael S
MS
Raposo
Graça
G
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
D033961:Adaptor Protein Complex 1; D033963:Adaptor Protein Complex 3; D021382:Protein Sorting Signals; D014442:Monophenol Monooxygenase