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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen mpi-cbg 2003     Display Documents

ID: 15457.0, MPI für molekulare Zellbiologie und Genetik / Publikationen mpi-cbg 2003
Role of Rab5 in the recruitment of hVps34/p150 to the early endosome
Authors:Murray, J. T.; Panaretou, C.; Stenmark, H.; Miaczynska, M.; Backer, J. M.
Date of Publication (YYYY-MM-DD):2002-06
Title of Journal:Traffic
Journal Abbrev.:Traffic
Issue / Number:6
Start Page:416
End Page:427
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:PI 3-kinases are important regulators of endocytic trafficking. We have previously proposed a model in which the Rab5 GTPase recruits EEA1 to the early endosome both directly, by binding to EEA1, and indirectly, through the recruitment of the p150/hVps34 PI 3-kinase and the production of PI[3]P in the endosomal membrane. In this study we have examined this model in vivo. We find that both endogenous hVps34 and p150 are targeted to enlarged endosomal structures in cells expressing constitutively activated Rab5, where they are significantly colocalized with EEA1. Recombinant fragments of p150 disrupt the endosomal localization of EEA1, showing that p150 is required for EEA1 targeting. We further analyzed the mechanism of GTP-dependent Rab5-p150 binding, and showed the p150 HEAT and WD40 domains are required for binding, whereas deletion of the protein kinase domain increases binding to Rab5. Overexpression of constitutively active Rab5 caused a redistribution of epitope-tagged hVps34 and p150 to Rab5- positive endosomes. However, subcellular fractionation showed that this was not due to a significant recruitment of hVps34 or p150 from the cytosolic to the particulate fraction. These data suggest that the binding of Rab5 to the HEAT/WD40 domains of p150 is important in regulating the localization of hVps34/p150. However, Rab5 does not appear to act by directly recruiting p150/hVps34 complexes from the cytosol to the endosomal membrane.
Free Keywords:EEA1; endosome; p150; Rab5; Vps34
Comment of the Author/Creator:Date: 2002, JUN
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für molekulare Zellbiologie und Genetik
External Affiliations:Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467, USA; Imperial Canc Res Fund, London WC2A 3PX, England; Norwegian Radium Hosp, Oslo, Norway;
Identifiers:ISI:000175894200005 [ID No:1]
ISSN:1398-9219 [ID No:2]
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