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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. (2001-03-05) A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. Journal of Cell Biology, 152 5: 1057-1070.
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| Author(s) |
Pol, Albert
Luetterforst, Robert
Lindsay, Margaret
Heino, Sanna
Ikonen, Elina
Parton, Robert G.
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| Title |
A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance
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| Journal name |
Journal of Cell Biology
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| Publication date |
2001-03-05
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| Volume number |
152
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| Issue number |
5
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| ISSN |
0021-9525
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| Start page |
1057
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| End page |
1070
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| Total pages |
14
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| Place of publication |
New York
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| Publisher |
The Rockefeller University Press
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| Collection year |
2001
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| Subject |
C1
270100 Biochemistry and Cell Biology
730106 Cardiovascular system and diseases
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| 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.
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| Keyword(s) |
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
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| Additional Notes |
DOI: 10.1083/jcb.152.5.1057
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