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PMID: 12221119 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Modulation of cellular cholesterol transport and homeostasis by Rab11.

Molecular biology of the cell ·Vol. 13 ·No. 9 ·2002-09-00 ·Pages 3107-22

Hölttä-Vuori M, Tanhuanpää K, Möbius W, Somerharju P, Ikonen E

Abstract

To analyze the contribution of vesicular trafficking pathways in cellular cholesterol transport we examined the effects of selected endosomal Rab proteins on cholesterol distribution by filipin staining. Transient overexpression of Rab11 resulted in prominent accumulation of free cholesterol in Rab11-positive organelles that sequestered transferrin receptors and internalized transferrin. Sphingolipids were selectively redistributed as pyrene-sphingomyelin and sulfatide cosequestered with Rab11-positive endosomes, whereas globotriaosyl ceramide and GM2 ganglioside did not. Rab11 overexpression did not perturb the transport of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine-perchlorate-labeled low-density lipoprotein (LDL) to late endosomes or the Niemann-Pick type C1 (NPC1)-induced late endosomal cholesterol clearance in NPC patient cells. However, Rab11 overexpression inhibited cellular cholesterol esterification in an LDL-independent manner. This effect could be overcome by introducing cholesterol to the plasma membrane by using cyclodextrin as a carrier. These results suggest that in Rab11-overexpressing cells, deposition of cholesterol in recycling endosomes results in its impaired esterification, presumably due to defective recycling of cholesterol to the plasma membrane. The findings point to the importance of the recycling endosomes in regulating cholesterol and sphingolipid trafficking and cellular cholesterol homeostasis.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Biological Transport Biotin/metabolism Blotting, Western COS Cells Carrier Proteins/metabolism Cholesterol/metabolism Cyclodextrins/metabolism Endocytosis Endosomes/metabolism GTP Phosphohydrolases/metabolism Genes, Dominant Green Fluorescent Proteins Immunohistochemistry Intracellular Signaling Peptides and Proteins Lipoproteins, LDL/metabolism Luminescent Proteins/metabolism Membrane Glycoproteins/metabolism Microscopy, Fluorescence Mutation Niemann-Pick C1 Protein Phenotype Receptors, Transferrin/metabolism Time Factors Transfection Transferrin/metabolism Xanthenes/pharmacology rab GTP-Binding Proteins/metabolism
Chemicals
Carrier Proteins Cyclodextrins Intracellular Signaling Peptides and Proteins Lipoproteins, LDL Luminescent Proteins Membrane Glycoproteins NPC1 protein, human Niemann-Pick C1 Protein Receptors, Transferrin Transferrin Xanthenes Green Fluorescent Proteins Biotin Texas red Adenosine Triphosphate Cholesterol GTP Phosphohydrolases rab11 protein rab GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hölttä-Vuori Maarit
Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Finland.
Tanhuanpää Kimmo
Möbius Wiebke
Somerharju Pentti
Ikonen Elina
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-01-0025
Published
2002-09-00
Pages
3107-22
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC124146
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e02-01-0025 PMC Full Text View journal details
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