Late Endosomal Cholesterol Accumulation Leads to Impaired Intra-Endosomal Trafficking

Sobo, Komla, Le Blanc, Isabelle, Luyet, Pierre-Philippe, Fivaz, Marc, Ferguson, Charles, Parton, Robert G., Gruenberg, Jean and van der Goot, F. Gisou (2007) Late Endosomal Cholesterol Accumulation Leads to Impaired Intra-Endosomal Trafficking. PLoS One, 2 9: e851. doi:10.1371/journal.pone.0000851


Author Sobo, Komla
Le Blanc, Isabelle
Luyet, Pierre-Philippe
Fivaz, Marc
Ferguson, Charles
Parton, Robert G.
Gruenberg, Jean
van der Goot, F. Gisou
Title Late Endosomal Cholesterol Accumulation Leads to Impaired Intra-Endosomal Trafficking
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2007-09-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0000851
Open Access Status DOI
Volume 2
Issue 9
Start page e851
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Background.
Pathological 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 Findings.
Cholesterol 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/Significance.

These results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 63 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 60 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 10 Sep 2011, 06:28:01 EST by System User on behalf of Institute for Molecular Bioscience