Protein networks supporting AP-3 function in targeting lysosomal membrane proteins

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Thorsten Baust - , Technische Universität Dresden (Autor:in)
  • Mihaela Anitei - , Technische Universität Dresden (Autor:in)
  • Cornelia Czupalla - , Technische Universität Dresden (Autor:in)
  • Iryna Parshyna - , Technische Universität Dresden (Autor:in)
  • Line Bourel - (Autor:in)
  • Christoph Thiele - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Eberhard Krause - (Autor:in)
  • Bernard Hoflack - , Technische Universität Dresden (Autor:in)

Abstract

The AP-3 adaptor complex targets selected transmembrane proteins to lysosomes and lysosome-related organelles. We reconstituted its preferred interaction with liposomes containing the ADP ribosylation factor (ARF)-1 guanosine triphosphatase (GTPase), specific cargo tails, and phosphatidylinositol-3 phosphate, and then we performed a proteomic screen to identify new proteins supporting its sorting function. We identified ≈30 proteins belonging to three networks regulating either AP-3 coat assembly or septin polymerization or Rab7-dependent lysosomal transport. RNA interference shows that, among these proteins, the ARF-1 exchange factor brefeldin A-inhibited exchange factor 1, the ARF-1 GTPase-activating protein 1, the Cdc42-interacting Cdc42 effector protein 4, an effector of septin-polymerizing GTPases, and the phosphatidylinositol-3 kinase IIIC3 are key components regulating the targeting of lysosomal membrane proteins to lysosomes in vivo. This analysis reveals that these proteins, together with AP-3, play an essential role in protein sorting at early endosomes, thereby regulating the integrity of these organelles.

Details

OriginalspracheEnglisch
Seiten (von - bis)1942-1951
Seitenumfang10
FachzeitschriftMolecular Biology of the Cell
Jahrgang19
Ausgabenummer5
PublikationsstatusVeröffentlicht - Mai 2008
Peer-Review-StatusJa

Externe IDs

PubMed 18287518

Schlagworte

ASJC Scopus Sachgebiete