INTRACELLULAR CHOLESTEROL TRANSPORT

Recent data on the roles of vesicle- and 'raft'-mediated pathways in i ntracellular free cholesterol (FC) transport are reviewed. Cholesterol internalized from plasma lipoproteins is transferred via endocytic ve sicles to the trans-Golgi network (TGN), consistent with prior data in dicating a key role for this organelle in protein and lipid sorting an d transport. Newly synthesized and lipoprotein-derived FC are returned to the cell surface by a common raft-dependent pathway. Intracellular FC transport promotes the delivery of GPI-anchored proteins to the ce ll surface; it is also an additional mechanism to regulate cell FC con tent. Many peripheral cells express caveolin, an FC-binding protein lo calized to plasma membrane caveolae. FC delivery to cell surface caveo lae is accelerated by caveolin. Caveolar FC becomes targeted to small, lipid-poor (prebeta-) high density lipoprotein particles. Caveolin ma y protect quiescent cells, regulating FC efflux more efficiently in re sponse to changing medium lipoprotein concentrations. Overall, these r ecent findings suggest that cell FC content can be regulated at the le vels of both influx and efflux, and indicate key roles for the TGN and in cells expressing caveolin, cell-surface caveolae.