Sterol and lipid trafficking in mammalian cells.

The pathways involved in the intracellular transport and distribution of lipids in general, and sterols in particular, are poorly understood. Cholesterol plays a major role in modulating membrane bilayer structure and important cellular functions, including signal transduction and membrane trafficking. Both the overall cholesterol content of a cell, as well as its distribution in specific organellar membranes are stringently regulated. Several diseases, many of which are incurable at present, have been characterized as results of impaired cholesterol transport and/or storage in the cells. Despite their importance, many fundamental aspects of intracellular sterol transport and distribution are not well understood. For instance, the relative roles of vesicular and non-vesicular transport of cholesterol have not yet been fully determined, nor are the non-vesicular transport mechanisms well characterized. Similarly, whether cholesterol is asymmetrically distributed between the two leaflets of biological membranes, and if so, how this asymmetry is maintained, is poorly understood. In this review, we present a summary of the current understanding of these aspects of intracellular trafficking and distribution of lipids, and more specifically, of sterols.

[1]  James H. Hurley,et al.  Structural mechanism for sterol sensing and transport by OSBP-related proteins , 2005, Nature.

[2]  Richard G. W. Anderson,et al.  A Role for Caveolin in Transport of Cholesterol from Endoplasmic Reticulum to Plasma Membrane* , 1996, The Journal of Biological Chemistry.

[3]  S. Veatch,et al.  A closer look at the canonical 'Raft Mixture' in model membrane studies. , 2003, Biophysical journal.

[4]  F. Maxfield,et al.  Role of Membrane Organization and Membrane Domains in Endocytic Lipid Trafficking , 2000, Traffic.

[5]  T. Steck,et al.  Probing red cell membrane cholesterol movement with cyclodextrin. , 2002, Biophysical journal.

[6]  Y. Ying,et al.  Characterization of a Cytosolic Heat-shock Protein-Caveolin Chaperone Complex , 1998, The Journal of Biological Chemistry.

[7]  V. Puri,et al.  Membrane Traffic in Sphingolipid Storage Diseases , 2000, Traffic.

[8]  D. Stocco.  StAR protein and the regulation of steroid hormone biosynthesis. , 2001, Annual review of physiology.

[9]  R. DeGrella,et al.  Intracellular transport of cholesterol to the plasma membrane. , 1982, The Journal of biological chemistry.

[10]  F. Maxfield,et al.  Vesicular and Non-vesicular Sterol Transport in Living Cells , 2002, The Journal of Biological Chemistry.

[11]  F. Maxfield,et al.  Effects of Cholesterol Depletion and Increased Lipid Unsaturation on the Properties of Endocytic Membranes*[boxs] , 2004, Journal of Biological Chemistry.

[12]  S. Dodd,et al.  Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by (2)H NMR spectroscopy. , 2000, Biophysical journal.

[13]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[14]  F. Maxfield,et al.  Cholesterol depletion induces large scale domain segregation in living cell membranes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[15]  L. Liscum,et al.  Intracellular cholesterol transport. , 1992, Journal of lipid research.

[16]  E. J. Reschly,et al.  Sterol Carrier Protein-2 Overexpression Enhances Sterol Cycling and Inhibits Cholesterol Ester Synthesis and High Density Lipoprotein Cholesterol Secretion* , 1997, The Journal of Biological Chemistry.

[17]  E. Ikonen,et al.  Dissecting the role of the golgi complex and lipid rafts in biosynthetic transport of cholesterol to the cell surface. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Rigotti,et al.  Sterol Carrier Protein-2 Is Involved in Cholesterol Transfer from the Endoplasmic Reticulum to the Plasma Membrane in Human Fibroblasts (*) , 1995, The Journal of Biological Chemistry.

[19]  R. Parton,et al.  Caveolin, cholesterol, and lipid bodies. , 2005, Seminars in cell & developmental biology.

[20]  F. Schroeder,et al.  Sterol Carrier Protein-2, a New Fatty Acyl Coenzyme A-binding Protein* , 1996, The Journal of Biological Chemistry.

[21]  F. Maxfield,et al.  Role of cholesterol and lipid organization in disease , 2005, Nature.

[22]  A. Uittenbogaard,et al.  Palmitoylation of Caveolin-1 Is Required for Cholesterol Binding, Chaperone Complex Formation, and Rapid Transport of Cholesterol to Caveolae* , 2000, The Journal of Biological Chemistry.

[23]  S. Gummadi,et al.  Chemical modification identifies two populations of glycerophospholipid flippase in rat liver ER. , 2004, Biochemistry.

[24]  J. Mancias,et al.  Exiting the Endoplasmic Reticulum , 2005, Traffic.

[25]  E. London.  Insights into lipid raft structure and formation from experiments in model membranes. , 2002, Current opinion in structural biology.

[26]  A. Menon.  Introduction: lipid transport--an overview. , 2002, Seminars in cell & developmental biology.

[27]  W. Prinz.  Cholesterol trafficking in the secretory and endocytic systems. , 2002, Seminars in cell & developmental biology.

[28]  E. Rodriguez-Boulan,et al.  Protein sorting in the Golgi complex: shifting paradigms. , 2005, Biochimica et biophysica acta.

[29]  H. Mcconnell,et al.  Condensed complexes of cholesterol and phospholipids. , 2003, Biophysical journal.

[30]  W. Hong.  SNAREs and traffic. , 2005, Biochimica et biophysica acta.

[31]  J. Freed,et al.  New method for determining tie-lines in coexisting membrane phases using spin-label ESR. , 2005, Biochimica et biophysica acta.

[32]  E. Ikonen,et al.  Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis. , 2005, The Biochemical journal.

[33]  J. Breslow,et al.  Intracellular Cholesterol Transport , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[34]  F. Maxfield,et al.  Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog. , 1998, Biophysical journal.

[35]  R. Pagano,et al.  Endocytosis and sorting of glycosphingolipids in sphingolipid storage disease. , 2002, Trends in cell biology.

[36]  Sushmita Mukherjee,et al.  Endocytic Sorting of Lipid Analogues Differing Solely in the Chemistry of Their Hydrophobic Tails , 1999, The Journal of cell biology.

[37]  P. Hylemon,et al.  Human StarD5, a cytosolic StAR-related lipid binding protein Published, JLR Papers in Press, May 16, 2005. DOI 10.1194/jlr.M400501-JLR200 , 2005, Journal of Lipid Research.

[38]  F. Maxfield,et al.  Direct Observation of Rapid Internalization and Intracellular Transport of Sterol by Macrophage Foam Cells , 2005, Traffic.

[39]  Satoshi Yasuda,et al.  Molecular machinery for non-vesicular trafficking of ceramide , 2003, Nature.

[40]  F. Maxfield,et al.  Intracellular cholesterol transport , 2002, The Journal of clinical investigation.

[41]  J. Hurley,et al.  Structure and lipid transport mechanism of a StAR-related domain , 2000, Nature Structural Biology.

[42]  P. Yeagle.  Cholesterol and the cell membrane. , 1985, Biochimica et biophysica acta.

[43]  R. Pagano,et al.  Use of fluorescent sphingolipid analogs to study lipid transport along the endocytic pathway. , 2005, Methods.

[44]  F. Schroeder,et al.  Transmembrane distribution of sterol in the human erythrocyte. , 1991, Biochimica et biophysica acta.

[45]  A. Menon,et al.  Transport of newly synthesized sterol to the sterol-enriched plasma membrane occurs via nonvesicular equilibration. , 2005, Biochemistry.

[46]  A. Bist,et al.  Intracellular cholesterol transport in synchronized human skin fibroblasts. , 1999, Biochemistry.