Journal ArticleDOI
EEA1 links PI(3)K function to Rab5 regulation of endosome fusion
Anne Simonsen,Roger Lippé,Savvas Christoforidis,Jean Michel Gaullier,Andreas Brech,Judy M. Callaghan,Ban-Hock Toh,Carol Murphy,Carol Murphy,Marino Zerial,Harald Stenmark +10 more
Reads0
Chats0
TLDR
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 EEA 1 may confer directionality to Rab5-dependent endocytic transport.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.read more
Citations
More filters
Journal ArticleDOI
Rab proteins as membrane organizers
Marino Zerial,Heidi M. McBride +1 more
TL;DR: Cellular organelles in the exocytic and endocytic pathways have a distinctive spatial distribution and communicate through an elaborate system of vesiculo-tubular transport.
Journal ArticleDOI
Rab GTPases as coordinators of vesicle traffic.
TL;DR: Crosstalk between multiple Rab GTPases through shared effectors, or through effectors that recruit selective Rab activators, ensures the spatiotemporal regulation of vesicle traffic.
Journal ArticleDOI
Small GTP-Binding Proteins
TL;DR: In this review, functions of small G proteins and their modes of activation and action are described.
Journal ArticleDOI
Role of Rab GTPases in membrane traffic and cell physiology.
Alex H. Hutagalung,Peter Novick +1 more
TL;DR: This review discusses how Rabs can regulate virtually all steps of membrane traffic from the formation of the transport vesicle at the donor membrane to its fusion at the target membrane.
Journal ArticleDOI
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
TL;DR: This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.
References
More filters
Journal ArticleDOI
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
TL;DR: In this article, six monoclonal antibodies have been isolated from mice immunized with synthetic peptide immunogens whose sequences are derived from that of the human c-myc gene product.
Journal ArticleDOI
Mammalian Ras interacts directly with the serine/threonine kinase Raf
TL;DR: Raf interacts with wild-type and activated Ras, but not with an effector domain mutant of Ras or with a dominant-interfering Ras mutant, and this interaction is dependent on GTP bound to Ras.
Journal ArticleDOI
The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway.
Cecilia Bucci,Robert G. Parton,Ian H. Mather,Henk Stunnenberg,Kai Simons,Bernard Hoflack,Marino Zerial +6 more
TL;DR: It is concluded that rab5 is a rate-limiting component of the machinery regulating the kinetics of membrane traffic in the early endocytic pathway.
Journal ArticleDOI
Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.
TL;DR: Findings provide evidence that members of the YPT1/SEC4 subfamily of GTP binding proteins are localized to specific exocytic and endocytic subcompartments in mammalian cells.
Journal ArticleDOI
rab5 controls early endosome fusion in vitro.
TL;DR: In vitro findings strongly suggest that rab5 is involved in the process of early endosome fusion, and the inhibition mediated by anti-rab5 antibodies could be overcome by complementing the assay with the cytosol containing wild-type rab5, but not with the same cytOSol depleted of rab5.