EEA1 links PI(3)K function to rab5 regulation of endosome fusion.
Research output: Contribution to journal › Article › peer-review
Authors
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 language | English |
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Pages (from-to) | 494-498 |
Number of pages | 5 |
Journal | Nature |
Volume | 394 |
Publication status | Published - 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