title: Fission of tubular endosomes triggers endosomal acidification and movement.
abstract: The early endosome acts as a sorting station for internalized molecules destined for recycling or degradation. While recycled molecules are sorted and delivered to tubular endosomes, residual compartments containing molecules to be degraded undergo "maturation" before final degradation in the lysosome. This maturation involves acidification, microtubule-dependent motility, and perinuclear localization. It is currently unknown how sorting and the processes of maturation cooperate with each other. Here, we show that fission of a tubular endosome triggers the maturation of the residual endosome, leading to degradation. Use of the dynamin inhibitor dynasore to block tubular endosome fission inhibited acidification, endosomal motility along microtubules, perinuclear localization, and degradation. However, tubular endosome fission was not affected by inhibiting endosomal acidification or by depolymerizing the microtubules. These results demonstrate that the fission of recycling tubules is the first important step in endosomal maturation and degradation in the lysosome. We believe this to be the first evidence of a cascade from sorting to degradation.
authors.affiliation: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Mesaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanabe
authors.forename: Masanori
authors.initials: M
authors.lastname: Obayashi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Oe
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
mesh_terms: D000143:Acids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009068:Movement / Q000187:drug effects; D014168:Transferrin / Q000378:metabolism
chemical_list: D000143:Acids; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D014168:Transferrin; D004815:Epidermal Growth Factor