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Membrane Cholesterol, Lateral Mobility, and the Phosphatidylinositol 4,5-Biphosphate-Dependent Organization of Cell Actin

Jeanne Kwik, Sarah Boyle, David Fooksman, Leonid Margolis, Michael P. Sheetz and Michael Edidin
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 24 (Nov. 25, 2003), pp. 13964-13969
Stable URL: http://www.jstor.org/stable/3148895
Page Count: 6
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Membrane Cholesterol, Lateral Mobility, and the Phosphatidylinositol 4,5-Biphosphate-Dependent Organization of Cell Actin
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Abstract

Responses to cholesterol depletion are often taken as evidence of a role for lipid rafts in cell function. Here, we show that depletion of cell cholesterol has global effects on cell and plasma membrane architecture and function. The lateral mobility of membrane proteins is reduced when cell cholesterol is chronically or acutely depleted. The change in mobility is a consequence of the reorganization of the cell actin. Binding of a GFP-tagged pleckstrin homology domain specific for phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to the plasma membrane is reduced after cholesterol depletion. This result implies that the reorganization of cytoskeleton depends on the loss or redistribution of plasma membrane PI(4,5)P2. Consistent with this observation, agents that sequester plasma membrane PI(4,5)P2 mimic the effects of cholesterol depletion on actin organization and on lateral mobility.

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