Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes

Mol Biol Cell. 2005 Nov;16(11):5356-72. doi: 10.1091/mbc.e05-07-0626. Epub 2005 Sep 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 1 / physiology*
  • Adaptor Protein Complex 3 / physiology*
  • Amino Acid Sequence
  • Animals
  • Endosomes / metabolism*
  • Humans
  • Melanocytes / metabolism
  • Melanocytes / ultrastructure
  • Melanosomes / metabolism*
  • Mice
  • Microscopy, Electron
  • Molecular Sequence Data
  • Monophenol Monooxygenase / metabolism*
  • Protein Sorting Signals
  • Protein Transport
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Adaptor Protein Complex 1
  • Adaptor Protein Complex 3
  • Protein Sorting Signals
  • Monophenol Monooxygenase