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

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

Research output: Contribution to journalArticlepeer-review

882 Citations (Scopus)


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


  • 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


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