A ROLE FOR CAVEOLIN IN TRANSPORT OF CHOLESTEROL FROM ENDOPLASMIC-RETICULUM TO PLASMA-MEMBRANE

Caveolin is a 22-kDa membrane protein found associated with a coat mat erial decorating the inner membrane surface of caveolae. A remarkable feature of this protein is its ability to migrate from caveolae direct ly to the endoplasmic reticulum (ER) when membrane cholesterol is oxid ized. We now present evidence caveolin is involved in transporting new ly synthesized cholesterol from the ER directly to caveolae. MA104 cel ls and normal human fibroblasts transported new cholesterol to caveola e with a half-time of similar to 10 min. The cholesterol then rapidly flowed from caveolae to non-caveolae membrane. Cholesterol moved out o f caveolae even when the supply of fresh cholesterol from the ER was i nterrupted. Treatment of cells with 10 mu g/ml progesterone blocked ch olesterol movement from ER to caveolae. Simultaneously, caveolin accum ulated in the lumen of the ER, suggesting cholesterol transport is lin ked to caveolin movement. Caveolae fractions from cells expressing cav eolin were enriched in cholesterol 3-4-fold, while the same fractions from cells lacking caveolin were not enriched. Cholesterol transport t o the cell surface was nearly 4 times more rapid in cells expressing c aveolin than in matched cells lacking caveolin.