EEA1 links PI(3)K function to rab5 regulation of endosome fusion.

Research output: Contribution to journalArticlepeer-review

Authors

  • A. Simonsen
  • R. Lippe
  • S. Christoforidis
  • J-M. Gaullier
  • A. Brech
  • J. Callaghan
  • B-H. Toh
  • M. Zerial
  • H. Stenmark

Colleges, School and Institutes

Abstract

GTPases and lipid kinases regulate membrane traffic along the endocytic pathway by mechanisms that are not completely understood. Fusion between early endosomes requires phosphatidylinositol-3-OH kinase (PI(3)K) activity as well as the small GTPase Rab5. Excess Rab5-GTP complex restores endosome fusion when PI(3)K is inhibited. Here we identify the early-endosomal autoantigen EEA1 which binds the PI(3)K product phosphatidylinositol-3-phosphate, as a new Rab5 effector that is required for endosome fusion. The association of EEA1 with the endosomal membrane requires Rab5-GTP and PI(3)K activity, and excess Rab5-GTP stabilizes the membrane association of EEA1 even when PI(3)K is inhibited. The identification of EEA1 as a direct Rab5 effector provides a molecular link between PI(3)K and Rab5, and its restricted distribution to early endosomes indicates that EEA1 may confer directionality to Rab5-dependent endocytic transport.

Details

Original languageEnglish
Pages (from-to)494-498
Number of pages5
JournalNature
Volume394
Publication statusPublished - 1998

Keywords

  • 1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors/*physiology Androstadienes/pharmacology Animal Autoantigens/physiology Cattle Cell Line Cloning, Molecular Endosomes/*physiology Enzyme Inhibitors/pharmacology GTP-Binding Proteins/genetics/*physiology Guanosine Triphosphate/physiology Hamsters Hela Cells Human Intracellular Membranes/physiology Membrane Fusion/*physiology Membrane Proteins/genetics/*physiology Mutagenesis Recombinant Fusion Proteins/metabolism Support, Non-U.S. Gov't rab5 GTP-Binding Proteins/*metabolism