A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance

Pol, Albert, Luetterforst, Robert, Lindsay, Margaret, Heino, Sanna, Ikonen, Elina and Parton, Robert G. (2001) A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. Journal of Cell Biology, 152 5: 1057-1070.


Author Pol, Albert
Luetterforst, Robert
Lindsay, Margaret
Heino, Sanna
Ikonen, Elina
Parton, Robert G.
Title A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance
Journal name Journal of Cell Biology   Check publisher's open access policy
ISSN 0021-9525
Publication date 2001-03-05
Sub-type Article (original research)
DOI 10.1083/jcb.152.5.1057
Volume 152
Issue 5
Start page 1057
End page 1070
Total pages 14
Place of publication New York
Publisher The Rockefeller University Press
Collection year 2001
Language eng
Subject C1
270100 Biochemistry and Cell Biology
730106 Cardiovascular system and diseases
Abstract Recent studies have indicated a role for caveolin in regulating cholesterol-dependent signaling events. In the present study we have analyzed the role of caveolins in intracellular cholesterol cycling using a dominant negative caveolin mutant. The mutant caveolin protein, cav-3(DGV) specifically associates with the membrane surrounding large lipid droplets. These structures contain neutral lipids, and are accessed by caveolin 1-3 upon overexpression. Fluorescence, electron, and video microscopy observations are consistent with formation of the membrane-enclosed lipid rich structures by maturation of subdomains of the ER. The caveolin mutant causes the intracellular accumulation of free cholesterol (FC) in late endosomes, a decrease in surface cholesterol and a decrease in cholesterol efflux and synthesis. The amphiphile U18666A acts synergistically with cav(DGV) to increase intracellular accumulation of FC. Incubation of cells with oleic acid induces a significant accumulation of full-length caveolins in the enlarged lipid droplets. We conclude that caveolin can associate with the membrane surrounding lipid droplets and is a key component involved in intracellular cholesterol balance and lipid transport in fibroblasts.
Keyword Cell Biology
Caveolin
Caveolae
Cholesterol
Lipid Droplets
Endoplasmic Reticulum
Trans-golgi-network
Plasma-membrane
Endoplasmic-reticulum
Chaperone Complex
Binding Protein
Mdck Cells
Localization
Pathway
Identification
Compartment
Q-Index Code C1
Additional Notes DOI: 10.1083/jcb.152.5.1057

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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Created: Tue, 14 Aug 2007, 16:52:13 EST