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

Abstract:

: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.

journal_name

Nature

journal_title

Nature

authors

Zeigerer A,Gilleron J,Bogorad RL,Marsico G,Nonaka H,Seifert S,Epstein-Barash H,Kuchimanchi S,Peng CG,Ruda VM,Del Conte-Zerial P,Hengstler JG,Kalaidzidis Y,Koteliansky V,Zerial M

doi

10.1038/nature11133

subject

Has Abstract

pub_date

2012-05-23 00:00:00

pages

465-70

issue

7399

eissn

0028-0836

issn

1476-4687

pii

nature11133

journal_volume

485

pub_type

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