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Science 1 December 2000:
Vol. 290. no. 5497, pp. 1721 - 1726
DOI: 10.1126/science.290.5497.1721

Review

How Cells Handle Cholesterol

Kai Simons,1* Elina Ikonen2

Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Recent advances suggest that cholesterol exerts many of its actions mainly by maintaining sphingolipid rafts in a functional state. How rafts contribute to cholesterol metabolism and transport in the cell is still an open issue. It has long been known that cellular cholesterol levels are precisely controlled by biosynthesis, efflux from cells, and influx of lipoprotein cholesterol into cells. The regulation of cholesterol homeostasis is now receiving a new focus, and this changed perspective may throw light on diseases caused by cholesterol excess, the prime example being atherosclerosis.

1 Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse, 01307 Dresden, Germany.
2 Department of Biochemistry, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland.
*   To whom correspondence should be addressed. E-mail: kai.simons{at}embl-heidelberg.de


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Caveolae: From Cell Biology to Animal Physiology.
B. Razani, S. E. Woodman, and M. P. Lisanti (2002)
Pharmacol. Rev. 54, 431-467
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Modulation of Cellular Cholesterol Transport and Homeostasis by Rab11.
M. Holtta-Vuori, K. Tanhuanpaa, W. Mobius, P. Somerharju, and E. Ikonen (2002)
Mol. Biol. Cell 13, 3107-3122
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Naturally Occurring Mutations in the Largest Extracellular Loops of ABCA1 Can Disrupt Its Direct Interaction with Apolipoprotein A-I.
M. L. Fitzgerald, A. L. Morris, J. S. Rhee, L. P. Andersson, A. J. Mendez, and M. W. Freeman (2002)
J. Biol. Chem. 277, 33178-33187
   Abstract »    Full Text »    PDF »
Multiple Functions of Sterols in Yeast Endocytosis.
A. Heese-Peck, H. Pichler, B. Zanolari, R. Watanabe, G. Daum, and H. Riezman (2002)
Mol. Biol. Cell 13, 2664-2680
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Self-assembling biomaterials: Liquid crystal phases of cholesteryl oligo(L-lactic acid) and their interactions with cells.
J. J. Hwang, S. N. Iyer, L.-S. Li, R. Claussen, D. A. Harrington, and S. I. Stupp (2002)
PNAS 99, 9662-9667
   Abstract »    Full Text »    PDF »
Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake.
A. L. Edinger and C. B. Thompson (2002)
Mol. Biol. Cell 13, 2276-2288
   Abstract »    Full Text »    PDF »
Loss of Plasma Membrane Phospholipid Asymmetry Requires Raft Integrity. ROLE OF TRANSIENT RECEPTOR POTENTIAL CHANNELS AND ERK PATHWAY.
C. Kunzelmann-Marche, J.-M. Freyssinet, and M. C. Martinez (2002)
J. Biol. Chem. 277, 19876-19881
   Abstract »    Full Text »    PDF »
Uncoupling of the Cholera Toxin-GM1 Ganglioside Receptor Complex from Endocytosis, Retrograde Golgi Trafficking, and Downstream Signal Transduction by Depletion of Membrane Cholesterol.
A. A. Wolf, Y. Fujinaga, and W. I. Lencer (2002)
J. Biol. Chem. 277, 16249-16256
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Heliothis virescens and Manduca sexta Lipid Rafts Are Involved in Cry1A Toxin Binding to the Midgut Epithelium and Subsequent Pore Formation.
M. Zhuang, D. I. Oltean, I. Gomez, A. K. Pullikuth, M. Soberon, A. Bravo, and S. S. Gill (2002)
J. Biol. Chem. 277, 13863-13872
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Regulation of cholesterol-7{alpha}-hydroxylase: BAREly missing a SHP.
R. A. Davis, J. H. Miyake, T. Y. Hui, and N. J. Spann (2002)
J. Lipid Res. 43, 533-543
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Membrane Restructuring via Ceramide Results in Enhanced Solute Efflux.
L. R. Montes, M. B. Ruiz-Arguello, F. M. Goni, and A. Alonso (2002)
J. Biol. Chem. 277, 11788-11794
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Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae.
T. Ringerike, F. D. Blystad, F. O. Levy, I. H. Madshus, and E. Stang (2002)
J. Cell Sci. 115, 1331-1340
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How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane.
L. G. Tilney, O. S. Harb, P. S. Connelly, C. G. Robinson, and C. R. Roy (2002)
J. Cell Sci. 114, 4637-4650
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