| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Departments of Physiology and Pharmacology and
Pathobiology, Texas A&M University, TVMC, College Station, Texas 77843
Cellular cholesterol homeostasis is a balance of influx, catabolism and synthesis, and efflux. Unlike vascular lipoprotein cholesterol transport, intracellular cholesterol trafficking is only beginning to be resolved. Exogenous cholesterol and cholesterol ester enter cells via the low-density lipoprotein (LDL) receptor/lysosomal and less so by nonvesicular, high-density lipoprotein (HDL) receptor/caveolar pathways. However, the mechanism(s) whereby cholesterol enters the lysosomal membrane, translocates, and transfers out of the lysosome to the cell interior are unknown. Likewise, the steps whereby cholesterol enters the cytofacial leaflet of the plasma membrane caveolae, rapidly translocates, leaves the exofacial leaflet, and transfers to extracellular HDL are unclear. Increasing evidence obtained with model and isolated cell membranes, transfected cells, genetic mutants, and gene-ablated mice suggests that proteins such as caveolin, sterol carrier protein-2 (SCP-2), Niemann-Pick C1 protein, steroidogenic acute regulatory protein (StAR), and other intracellular proteins mediate intracellular cholesterol transfer. While these proteins bind cholesterol and/or interact with cholesterol-rich membrane microdomains (e.g., caveolae, rafts, and annuli), their relative contributions to direct molecular versus vesicular cholesterol transfer remain to be resolved. The formation, regulation, and role of membrane microdomains in regulating cholesterol uptake/efflux and trafficking are unclear. Some cholesterol-binding proteins exert opposing effects on cellular cholesterol uptake/efflux, transfer of cholesterol out of the lysosomal membrane, and/or intracellular cholesterol trafficking to select membranous organelles. Resolving these cholesterol pathways and the role of membrane cholesterol microdomains is essential to our understanding not only of processes that affect cholesterol metabolism, but also of the abnormal regulation that may lead to disease (diabetes, obesity, atherosclerosis, neutral lipid storage, Niemann-Pick C, congenital lipoid adrenal hyperplasia, etc.).
Key Words: membrane • domain • caveolae • rafts • cholesterol • fatty acid • sterol carrier protein
This article has been cited by other articles:
|
|
 |
|
  A. Davalos, C. Fernandez-Hernando, F. Cerrato, J. Martinez-Botas, D. Gomez-Coronado, C. Gomez-Cordoves, and M. A. Lasuncion Red Grape Juice Polyphenols Alter Cholesterol Homeostasis and Increase LDL-Receptor Activity in Human Cells In Vitro J. Nutr., July 1, 2006; 136(7): 1766 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Martin, B. P. Atshaves, A. L. McIntosh, J. T. Mackie, A. B. Kier, and F. Schroeder Liver fatty acid binding protein gene ablation potentiates hepatic cholesterol accumulation in cholesterol-fed female mice Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G36 - G48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wu, H. Yang, W. Xiang, L. Zhou, M. Shi, G. Julies, J. M. LaPlante, B. R. Ballard, and Z. Guo Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice J. Lipid Res., July 1, 2005; 46(7): 1380 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wagner, A. Herwig, N. Azzouz, and H. D. Klenk Acylation-Mediated Membrane Anchoring of Avian Influenza Virus Hemagglutinin Is Essential for Fusion Pore Formation and Virus Infectivity J. Virol., May 15, 2005; 79(10): 6449 - 6458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Stover, A. Sharma, G. P. Robertson, and M. Kester Systemic Delivery of Liposomal Short-Chain Ceramide Limits Solid Tumor Growth in Murine Models of Breast Adenocarcinoma Clin. Cancer Res., May 1, 2005; 11(9): 3465 - 3474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Zaas, M. J. Duncan, G. Li, J. R. Wright, and S. N. Abraham Pseudomonas Invasion of Type I Pneumocytes Is Dependent on the Expression and Phosphorylation of Caveolin-2 J. Biol. Chem., February 11, 2005; 280(6): 4864 - 4872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Liu, H. Lu, Z. Jiang, A. Pastuszyn, and C.-a. A. Hu Apolipoprotein L6, a Novel Proapoptotic Bcl-2 Homology 3-Only Protein, Induces Mitochondria-Mediated Apoptosis in Cancer Cells Mol. Cancer Res., January 1, 2005; 3(1): 21 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ren, P. Hylemon, D. Marques, E. Hall, K. Redford, G. Gil, and W. M. Pandak Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis J. Lipid Res., November 1, 2004; 45(11): 2123 - 2131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Soccio and J. L. Breslow Intracellular Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1150 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Atshaves, H. R. Payne, A. L. McIntosh, S. E. Tichy, D. Russell, A. B. Kier, and F. Schroeder Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice J. Lipid Res., May 1, 2004; 45(5): 812 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, C. H. Ren, S. A. Tahir, C. Ren, and T. C. Thompson Caveolin-1 Maintains Activated Akt in Prostate Cancer Cells through Scaffolding Domain Binding Site Interactions with and Inhibition of Serine/Threonine Protein Phosphatases PP1 and PP2A Mol. Cell. Biol., December 15, 2003; 23(24): 9389 - 9404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yano, V. Rachochy, and J. L. Van Houten Glycosyl Phosphatidylinositol-Anchored Proteins in Chemosensory Signaling: Antisense Manipulation of Paramecium tetraurelia PIG-A Gene Expression Eukaryot. Cell, December 1, 2003; 2(6): 1211 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Sheffield and J. J. Gavinski Proteomics Methods for Probing Molecular Mechanisms in Signal Transduction J Dairy Sci, July 1, 2003; 86(13_suppl): E115 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Igbavboa, J. M. Pidcock, L. N. A. Johnson, T. M. Malo, A. E. Studniski, S. Yu, G. Y. Sun, and W. G. Wood Cholesterol Distribution in the Golgi Complex of DITNC1 Astrocytes Is Differentially Altered by Fresh and Aged Amyloid beta -Peptide-(1-42) J. Biol. Chem., May 2, 2003; 278(19): 17150 - 17157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Sheffield and J. J. Gavinski Proteomics methods for probing molecular mechanisms in signal transduction J Anim Sci, March 1, 2003; 81(suppl_3): 48 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. McIntosh, A. M. Gallegos, B. P. Atshaves, S. M. Storey, D. Kannoju, and F. Schroeder Fluorescence and Multiphoton Imaging Resolve Unique Structural Forms of Sterol in Membranes of Living Cells J. Biol. Chem., February 14, 2003; 278(8): 6384 - 6403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chao, M. Zhou, A. McIntosh, F. Schroeder, and A. B. Kier ACBP and cholesterol differentially alter fatty acyl CoA utilization by microsomal ACAT J. Lipid Res., January 1, 2003; 44(1): 72 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Atshaves, S. M. Storey, A. Petrescu, C. C. Greenberg, O. I. Lyuksyutova, R. Smith III, and F. Schroeder Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts Am J Physiol Cell Physiol, September 1, 2002; 283(3): C688 - C703. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
