Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins

J Cell Biol. 2004 Mar 29;164(7):1065-76. doi: 10.1083/jcb.200311064.

Abstract

The adaptor protein (AP) 3 adaptor complex has been implicated in the transport of lysosomal membrane proteins, but its precise site of action has remained controversial. Here, we show by immuno-electron microscopy that AP-3 is associated with budding profiles evolving from a tubular endosomal compartment that also exhibits budding profiles positive for AP-1. AP-3 colocalizes with clathrin, but to a lesser extent than does AP-1. The AP-3- and AP-1-bearing tubular compartments contain endocytosed transferrin, transferrin receptor, asialoglycoprotein receptor, and low amounts of the cation-independent mannose 6-phosphate receptor and the lysosome-associated membrane proteins (LAMPs) 1 and 2. Quantitative analysis revealed that of these distinct cargo proteins, only LAMP-1 and LAMP-2 are concentrated in the AP-3-positive membrane domains. Moreover, recycling of endocytosed LAMP-1 and CD63 back to the cell surface is greatly increased in AP-3-deficient cells. Based on these data, we propose that AP-3 defines a novel pathway by which lysosomal membrane proteins are transported from tubular sorting endosomes to lysosomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Animals
  • Cell Line
  • Cell Membrane / physiology
  • Endosomes / physiology*
  • Endosomes / ultrastructure
  • Kinetics
  • Lysosomes / physiology*
  • Lysosomes / ultrastructure
  • Membrane Proteins / metabolism*
  • Protein Transport
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / metabolism*
  • trans-Golgi Network / physiology
  • trans-Golgi Network / ultrastructure

Substances

  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Ap3d1 protein, mouse
  • Membrane Proteins
  • Transcription Factor AP-1
  • Transcription Factors