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Zeigerer, A.* ; Gilleron, J.* ; Bogorad, R.L.* ; Marsico, G.* ; Nonaka, H.* ; Seifert, S.* ; Epstein-Barash, H.* ; Kuchimanchi, S.* ; Peng, C.G.* ; Ruda, V.M.* ; del Conte-Zerial, P.* ; Hengstler, J.G.* ; Kalaidzidis, Y.* ; Koteliansky, V.* ; Zerial, M.*

Rab5 is necessary for the biogenesis of the endolysosomal system in vivo.

Nature 485, 465-470 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 485, Issue: 7399, Pages: 465-470 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)