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
Naturejournal_title
Natureauthors
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 Mdoi
10.1038/nature11133subject
Has Abstractpub_date
2012-05-23 00:00:00pages
465-70issue
7399eissn
0028-0836issn
1476-4687pii
nature11133journal_volume
485pub_type
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