Uptake and trafficking of exogenous sterols in Saccharomyces cerevisiae.

The proper distribution of sterols among organelles is critical for numerous cellular functions. How sterols are sorted and moved among membranes remains poorly understood, but they are transported not only in vesicles but also by non-vesicular pathways. One of these pathways moves exogenous sterols from the plasma membrane to the endoplasmic reticulum in the yeast Saccharomyces cerevisiae. We have found that two classes of proteins play critical roles in this transport, ABC transporters (ATP-binding-cassette transporters) and oxysterol-binding protein-related proteins. Transport is also regulated by phosphoinositides and the interactions of sterols with other lipids. Here, we summarize these findings and speculate on the role of non-vesicular sterol transfer in determining intracellular sterol distribution and membrane function.

[1]  W. Lehmann,et al.  Evidence for Segregation of Sphingomyelin and Cholesterol during Formation of Copi-Coated Vesicles , 2000, The Journal of cell biology.

[2]  Ping-yuan Wang,et al.  OSBP Is a Cholesterol-Regulated Scaffolding Protein in Control of ERK1/2 Activation , 2005, Science.

[3]  V. Olkkonen,et al.  Oxysterol binding proteins: in more than one place at one time? , 2004, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[4]  G. Daum,et al.  Multiple lipid transport pathways to the plasma membrane in yeast. , 2005, Biochimica et biophysica acta.

[5]  E. Chen,et al.  A fusion protein required for vesicle-mediated transport in both mammalian cells and yeast , 1989, Nature.

[6]  T. Levine,et al.  Multiple Pools of Phosphatidylinositol 4-Phosphate Detected Using the Pleckstrin Homology Domain of Osh2p* , 2004, Journal of Biological Chemistry.

[7]  J. Slotte.  Cholesterol-sphingomyelin interactions in cells--effects on lipid metabolism. , 1997, Sub-cellular biochemistry.

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

[9]  A. Munn,et al.  AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism , 2005, The EMBO journal.

[10]  J. Slotte,et al.  Depletion of plasma-membrane sphingomyelin rapidly alters the distribution of cholesterol between plasma membranes and intracellular cholesterol pools in cultured fibroblasts. , 1988, The Biochemical journal.

[11]  A. Tinkelenberg,et al.  Transcriptional Profiling Identifies Two Members of the ATP-binding Cassette Transporter Superfamily Required for Sterol Uptake in Yeast* , 2002, The Journal of Biological Chemistry.

[12]  R. D. Simoni,et al.  Cholesterol and vesicular stomatitis virus G protein take separate routes from the endoplasmic reticulum to the plasma membrane. , 1990, The Journal of biological chemistry.

[13]  W. Duan,et al.  Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae , 2005, The FEBS journal.

[14]  G. Prestwich,et al.  Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex , 2002, The Journal of cell biology.

[15]  M. Kaplan,et al.  Transport of cholesterol from the endoplasmic reticulum to the plasma membrane , 1985, The Journal of cell biology.

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

[17]  J. Rine,et al.  A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution , 2004, Journal of Cell Science.

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

[19]  J. Holthuis,et al.  Lipid traffic: floppy drives and a superhighway , 2005, Nature Reviews Molecular Cell Biology.

[20]  V. Olkkonen.  Oxysterol binding protein and its homologues: new regulatory factors involved in lipid metabolism , 2004, Current opinion in lipidology.

[21]  Ham.  Fast flip-flop of cholesterol and fatty acids in membranes: implications for membrane transport proteins , 2003 .

[22]  S. Munro,et al.  Dual targeting of Osh1p, a yeast homologue of oxysterol-binding protein, to both the Golgi and the nucleus-vacuole junction. , 2001, Molecular biology of the cell.

[23]  Kevin V. Shianna,et al.  A Mutation in a Purported Regulatory Gene Affects Control of Sterol Uptake in Saccharomyces cerevisiae , 1998, Journal of bacteriology.

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

[25]  W. Prinz,et al.  ATP-binding Cassette (ABC) Transporters Mediate Nonvesicular, Raft-modulated Sterol Movement from the Plasma Membrane to the Endoplasmic Reticulum* , 2004, Journal of Biological Chemistry.

[26]  J. Heinecke,et al.  ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. , 2005, Physiological reviews.

[27]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[28]  E. Leitner,et al.  Contribution of Are1p and Are2p to steryl ester synthesis in the yeast Saccharomyces cerevisiae. , 2000, European journal of biochemistry.

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

[30]  C. Vilchèze,et al.  Effect of the Structure of Natural Sterols and Sphingolipids on the Formation of Ordered Sphingolipid/Sterol Domains (Rafts) , 2001, The Journal of Biological Chemistry.

[31]  S. Sturley,et al.  Sterol homeostasis in the budding yeast, Saccharomyces cerevisiae. , 2005, Seminars in cell & developmental biology.

[32]  A. Rzhetsky,et al.  The human ATP-binding cassette (ABC) transporter superfamily. , 2001, Genome research.

[33]  J. Rine,et al.  Overlapping functions of the yeast oxysterol-binding protein homologues. , 2001, Genetics.

[34]  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.

[35]  P. Sluijs,et al.  How proteins move lipids and lipids move proteins , 2001, Nature Reviews Molecular Cell Biology.

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