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Science 1 December 2000: Vol. 290. no. 5497, pp. 1721 - 1726 DOI: 10.1126/science.290.5497.1721
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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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- Expression of a Novel, Sterol-Insensitive Form of Sterol Regulatory Element Binding Protein 2 (SREBP2) in Male Germ Cells Suggests Important Cell- and Stage-Specific Functions for SREBP Targets during Spermatogenesis.
- H. Wang, F. Liu, C. F. Millette, and D. L. Kilpatrick (2002)
Mol. Cell. Biol.
22, 8478-8490
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- Retarded Intracellular Lipid Transport Associated With Reduced Expression of Cdc42, a Member of Rho-GTPases, in Human Aged Skin Fibroblasts: A Possible Function of Cdc42 in Mediating Intracellular Lipid Transport.
- K. Tsukamoto, K.-i. Hirano, S. Yamashita, N. Sakai, C. Ikegami, Z. Zhang, F. Matsuura, H. Hiraoka, A. Matsuyama, M. Ishigami, et al. (2002)
Arterioscler. Thromb. Vasc. Biol.
22, 1899-1904
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- Palmitoylation of the Murine Leukemia Virus Envelope Protein Is Critical for Lipid Raft Association and Surface Expression.
- M. Li, C. Yang, S. Tong, A. Weidmann, and R. W. Compans (2002)
J. Virol.
76, 11845-11852
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- Localization of the Adhesion Receptor Glycoprotein Ib-IX-V Complex to Lipid Rafts Is Required for Platelet Adhesion and Activation.
- C. N. Shrimpton, G. Borthakur, S. Larrucea, M. A. Cruz, J.-F. Dong, and J. A. Lopez (2002)
J. Exp. Med.
196, 1057-1066
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- Role for Human Immunodeficiency Virus Type 1 Membrane Cholesterol in Viral Internalization.
- M. Guyader, E. Kiyokawa, L. Abrami, P. Turelli, and D. Trono (2002)
J. Virol.
76, 10356-10364
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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
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- 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
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- 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
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- 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
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- 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.
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J. Lipid Res.
43, 533-543
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- Membrane Restructuring via Ceramide Results in Enhanced Solute Efflux.
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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.
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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.
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J. Cell Sci.
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