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MBC in Press, published online ahead of print February 2, 2005
Mol. Biol. Cell 10.1091/mbc.E04-08-0737

A more recent version of this article appeared on April 1, 2005
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Submitted on August 25, 2004
Revised on January 18, 2005
Accepted on January 21, 2005

Cholesterol and Fatty Acids Regulate Dynamic Caveolin Trafficking through the Golgi Complex and between the Cell Surface and Lipid Bodies

Albert Pol,*{dagger} Sally Martin,* Manuel A. Fernández,{dagger} Mercedes Ingelmo-Torres,{dagger} Charles Ferguson,* Carlos Enrich,{dagger} and Robert G. Parton*

*Institute for Molecular Bioscience, Centre for Microscopy and Microanalysis and School of Biomedical Sciences, University of Queensland, Queensland 4072, Australia; {dagger}Departament de Biologia Cellular, Facultat de Medicina, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain

Monitoring Editor: Benjamin Glick

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 VSV-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.

Address correspondence to: Albert Pol (apols{at}ub.edu) or Robert G. Parton (R.Parton{at}imb.uq.edu.au)




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