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Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking.

Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking.

Authors :
Komla Sobo
Isabelle Le Blanc
Pierre-Philippe Luyet
Marc Fivaz
Charles Ferguson
Robert G Parton
Jean Gruenberg
F Gisou van der Goot
Source :
PLoS ONE, Vol 2, Iss 9, p e851 (2007)
Publication Year :
2007
Publisher :
Public Library of Science (PLoS), 2007.

Abstract

BackgroundPathological accumulation of cholesterol in late endosomes is observed in lysosomal storage diseases such as Niemann-Pick type C. We here analyzed the effects of cholesterol accumulation in NPC cells, or as phenocopied by the drug U18666A, on late endosomes membrane organization and dynamics.Methodology/principal findingsCholesterol accumulation did not lead to an increase in the raft to non-raft membrane ratio as anticipated. Strikingly, we observed a 2-3 fold increase in the size of the compartment. Most importantly, properties and dynamics of late endosomal intralumenal vesicles were altered as revealed by reduced late endosomal vacuolation induced by the mutant pore-forming toxin ASSP, reduced intoxication by the anthrax lethal toxin and inhibition of infection by the Vesicular Stomatitis Virus.Conclusions/significanceThese results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
2
Issue :
9
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.43679b340211428a86b4042b963ebf6f
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0000851