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Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles

Edgar, JR; Eden, ER; Futter, CE; (2014) Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic , 15 (2) 197- 211. 10.1111/tra.12139. Green open access

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Abstract

Multivesicular endosomes/bodies (MVBs) contain intraluminal vesicles (ILVs) that bud away from the cytoplasm. Multiple mechanisms of ILV formation have been identified, but the relationship between different populations of ILVs and MVBs remains unclear. Here we show in HeLa cells that different ILV subpopulations can be distinguished by size. EGF stimulation promotes the formation of large ESCRT-dependent ILVs, while depletion of the ESCRT-0 component, Hrs, promotes the formation of a uniformly sized population of small ILVs, the formation of which requires CD63. CD63 has previously been implicated in ESCRT-independent sorting of PMEL in MVBs and transfected PMEL is present on the small ILVs that form on Hrs depletion. Upregulation of CD63-dependent ILV formation by Hrs depletion indicates that Hrs and CD63 regulate competing machineries required for the generation of distinct ILV subpopulations. Taken together our results indicate that ILV size is influenced by their cargo and mechanism of formation and suggest a competitive relationship between ESCRT-dependent and -independent mechanisms of ILV formation within single MVBs.

Type: Article
Title: Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/tra.12139
Publisher version: http://dx.doi.org/10.1111/tra.12139
Language: English
Additional information: © 2013 The Authors. Traffic published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: CD63, Hrs, cholesterol, intraluminal vesicle, multivesicular endosome
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1443248
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