Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin

Jeanne Kwik, Sarah Boyle, David Fooksman, Leonid Margolis, Michael P. Sheetz, Michael Edidin

Research output: Contribution to journalArticle

369 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)13964-13969
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue numberSUPPL. 2
StatePublished - Nov 25 2003
Externally publishedYes


ASJC Scopus subject areas

  • General

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