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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2012-arch     Display Documents



ID: 645231.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2012-arch
Rab5 is necessary for the biogenesis of the endolysosomal system in vivo.
Authors:Zeigerer, Anja; Gilleron, Jerome; Bogorad, Roman L; Marsico, Giovanni; Nonaka, Hidenori; Seifert, Sarah; Epstein-Barash, Hila; Kuchimanchi, Satya; Peng, Chang Geng; Ruda, Vera M; Conte-Zerial, Perla Del; Hengstler, Jan G; Kalaidzidis, Yannis; Koteliansky, Victor; Zerial, Marino
Date of Publication (YYYY-MM-DD):2012
Title of Journal:Nature
Volume:485
Issue / Number:7399
Start Page:465
End Page:470
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.
External Publication Status:published
Document Type:Article
Communicated by:nn
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:4887
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