Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin.
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.
Kwik
Jeanne
J
Biology Department, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Boyle
Sarah
S
Fooksman
David
D
Margolis
Leonid
L
Sheetz
Michael P
MP
Edidin
Michael
M
D000199:Actins / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000199:Actins; D001798:Blood Proteins; D006680:HLA Antigens; D008563:Membrane Lipids; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C039077:platelet protein P47; D002784:Cholesterol