Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies

Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the...

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Veröffentlicht in:Molecular biology of the cell 2005-04, Vol.16 (4), p.2091-2105
Hauptverfasser: Pol, Albert, Martin, Sally, Fernández, Manuel A, Ingelmo-Torres, Mercedes, Ferguson, Charles, Enrich, Carlos, Parton, Robert G
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container_end_page 2105
container_issue 4
container_start_page 2091
container_title Molecular biology of the cell
container_volume 16
creator Pol, Albert
Martin, Sally
Fernández, Manuel A
Ingelmo-Torres, Mercedes
Ferguson, Charles
Enrich, Carlos
Parton, Robert G
description Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.
doi_str_mv 10.1091/mbc.e04-08-0737
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Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. 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subjects Animals
Aparell de Golgi
Caveolin 1
Caveolin 3
Caveolins - genetics
Caveolins - metabolism
Cell Membrane - drug effects
Cell Membrane - metabolism
Cells, Cultured
Cercopithecus aethiops
Cholesterol
Cholesterol - metabolism
Colesterol
Cricetinae
Fatty acids
Fatty Acids - metabolism
Golgi apparatus
Golgi Apparatus - drug effects
Golgi Apparatus - metabolism
Membrane proteins
Methanol - chemistry
Methanol - pharmacology
Microscopy, Video
Molecular Weight
Octoxynol - chemistry
Octoxynol - pharmacology
Protein Transport
Proteïnes de membrana
Solubility - drug effects
Temperature
Time Factors
Àcids grassos
title Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies
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