title: Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking.
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.
  
  
  RESULTS
  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
  These results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation.
authors.affiliation: Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Komla
authors.initials: K
authors.lastname: Sobo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Blanc
authors.forename: Pierre-Philippe
authors.initials: PP
authors.lastname: Luyet
authors.forename: Marc
authors.initials: M
authors.lastname: Fivaz
authors.forename: Charles
authors.initials: C
authors.lastname: Ferguson
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Jean
authors.initials: J
authors.lastname: Gruenberg
authors.forename: F Gisou
authors.initials: FG
authors.lastname: van der Goot
mesh_terms: D000818:Animals; D016466:CHO Cells; D002451:Cell Compartmentation; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D021381:Protein Transport