Caveolao are small, non-clathrin-coated plasma membrane invaginations I hat contain the structural protein, caveolin. In a variety of cell types, up to 50(rf of the total cellular phosphatidylinositol bisphosphate is found in the Sow density, detergent-resistant compartment that is also enriched in caveolin. It is this compartmentalized PIP2 that is subject to hormone-stimulated turnover. Other proteins involved in PI turnover including Gq and the EOF receptor are also localized in these low density domains suggesting that they may represent foci for hormone-stimulated PI Turnover in cells. Treatment of A43I cells with the cholesterol-binding agent, cyclodextrin, leads to the almost complete ablation of EOF- and bradykinin-stimulated PI turnover. However, EGF-stimulated autophosphorylation is not affected. This loss of hormone-responsiveness is associated with the delocalization of polyphosphoinositides out of the low density membrane domains. These data suggest that cholesterol-enriched membrane domains are required for hormone-stimulated PI hydrolysis at a level distal to EOF receptor kinase activation. Transfection of cells that normally lack caveo lae with a construct encoding caveolin leads to the production of numerous celi surface caveolae. The subcellular distribution of phosphoinositides and other signaling proteins is similar in caveolin-negative and caveolin expressing cells in dicating that caveolin is not required for the rompartmentalization of molecules involved in signal transduction. However, hormone-stimulated PI turnover wa-4 suppressed in caveolin-expressing cells suggesting that this protein may play a role in the regulation of PI turnover.
|State||Published - Dec 1 1998|