Specific regulation of the adaptor protein complex AP-3 by the Arf GAP AGAP1

Dev Cell. 2003 Sep;5(3):513-21. doi: 10.1016/s1534-5807(03)00234-x.


Arf1 regulates membrane trafficking at several membrane sites by interacting with at least seven different vesicle coat proteins. Here, we test the hypothesis that Arf1-dependent coats are independently regulated by specific interaction with Arf GAPs. We find that the Arf GAP AGAP1 directly associates with and colocalizes with AP-3, a coat protein complex involved in trafficking in the endosomal-lysosomal system. Binding is mediated by the PH domain of AGAP1 and the delta and sigma3 subunits of AP-3. Overexpression of AGAP1 changes the cellular distribution of AP-3, and reduced expression of AGAP1 renders AP-3 resistant to brefeldin A. AGAP1 overexpression does not affect the distribution of other coat proteins, and AP-3 distribution is not affected by overexpression of other Arf GAPs. Cells overexpressing AGAP1 also exhibit increased LAMP1 trafficking via the plasma membrane. Taken together, these results support the hypothesis that AGAP1 directly and specifically regulates AP-3-dependent trafficking.

Publication types

  • Comparative Study

MeSH terms

  • 3T3 Cells / drug effects
  • 3T3 Cells / metabolism
  • ADP-Ribosylation Factor 1 / physiology*
  • Adaptor Protein Complex 3 / metabolism*
  • Animals
  • Blotting, Western
  • Brefeldin A / pharmacology
  • Carrier Proteins / metabolism
  • Coatomer Protein / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique
  • GTPase-Activating Proteins / physiology*
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Precipitin Tests
  • Protein Multimerization
  • Protein Synthesis Inhibitors / pharmacology
  • Protein Transport / physiology*
  • RNA, Small Interfering / metabolism
  • Transfection
  • Yeasts


  • Adaptor Protein Complex 3
  • Carrier Proteins
  • Coatomer Protein
  • GTPase-Activating Proteins
  • Protein Synthesis Inhibitors
  • RNA, Small Interfering
  • Brefeldin A
  • ADP-Ribosylation Factor 1

Associated data

  • GENBANK/AB029022