title: Dynein is required for receptor sorting and the morphogenesis of early endosomes.
abstract: The early endosome is organised into domains to ensure the separation of cargo. Activated mitogenic receptors, such as epidermal growth factor (EGF) receptor, are concentrated into vacuoles enriched for the small GTPase Rab5, which progressively exclude nutrient receptors, such as transferrin receptor, into neighbouring tubules. These vacuoles become enlarged, increase their content of intralumenal vesicles as EGF receptor is sorted from the limiting membrane, and eventually mature to late endosomes. Maturation is governed by the loss of Rab5 and is accompanied by the movement of endosomes along microtubules towards the cell centre. Here, we show that EGF relocates to the cell centre in a dynein-dependent fashion, concomitant with the sorting away of transferrin receptor, although it remains in Rab5-positive early endosomes. When dynein function is acutely disrupted, efficient recycling of transferrin from EGF-containing endosomes is retarded, loss of Rab5 is slowed and endosome enlargement is reduced.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Driskell
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Mironov
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Allan
authors.forename: Philip G
authors.initials: PG
authors.lastname: Woodman
mesh_terms: D004398:Dyneins / Q000378:metabolism* / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism* / Q000502:physiology; D004815:Epidermal Growth Factor / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D008845:Microinjections; D008856:Microscopy, Fluorescence / Q000379:methods; D018715:Microscopy, Video / Q000379:methods; D009024:Morphogenesis; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014168:Transferrin / Q000493:pharmacokinetics; D033921:Vesicular Transport Proteins; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D011990:Receptors, Transferrin; D014168:Transferrin; D033921:Vesicular Transport Proteins; D004815:Epidermal Growth Factor; D004398:Dyneins; D020696:rab5 GTP-Binding Proteins