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Vol. 54, Issue 3, 431-468, September 2002
Department of Molecular Pharmacology, Albert Einstein College of
Medicine; and the Division of Hormone-Dependent Tumor Biology, Albert
Einstein Cancer Center, New York, New York
I. Introduction
II. Caveolae
A. Definition and Morphology
B. Tissue Specificity
C. Composition and Biochemical Properties
III. The Caveolin Gene Family
A. The Discovery of Caveolin and Its Relationship to Caveolae
B. The Other Caveolins (Caveolin-2 and -3)
C. Structural Properties of the Caveolins
1. Caveolin Membrane Topology.
2. Caveolin Oligomerization.
3. Structural Relationships between the Caveolins.
IV. Caveolar Biogenesis
A. The Role of Cholesterol
B. The Role of the Caveolins
V. Functional Significance of Caveolae/Caveolins
A. Vesicular Transport
1. Transcytosis.
2. Endocytosis.
3. Mechanisms of Endocytosis/Transcytosis.
4. Potocytosis.
B. Cellular Cholesterol Homeostasis
1. The Effect of Cholesterol on Caveolin-1.
2. Intracellular Transport of de Novo Synthesized
cholesterol.
3. Cholesterol Efflux from Cells.
C. Signal Transduction Mechanisms
1. Caveolae As Signalosomes: Compartmentalized
Signaling.
2. The Caveolins As Modulators of Signaling.
3. Caveolin-2 and -3 As Signaling Modulators.
4. Signaling Spotlight: Modulation of Endothelial Nitric-Oxide
Synthase Function.
5. Signaling Spotlight: the Dynamic Relationship of
G-Protein-Coupled Receptors and Caveolae.
D. Oncogenes and Tumorigenesis
1. Caveolae/Caveolins As Targets of Oncogenes.
2. The Caveolins As Tumor Suppressors.
3. Relevance to Human Cancers.
E. Specialized Functions: Caveolin-3 and Muscle Cells
F. Emerging Functions: Caveolins and Lipid Droplets
VI. Animal Models in the Study of Caveolae and Caveolins
A. Studies of Caveolin-1-Deficient Mice
1. Caveolin-1 and Caveolae Biogenesis.
2. Interactions of Caveolin-1 with the Other Caveolins.
3. Caveolin-1 and Cellular Proliferation.
4. Caveolin-1 and Endocytosis.
5. Caveolin-1 in the Lung.
6. The Vascular Physiology of Caveolin-1-Deficient
Mice.
7. Caveolin-1 and Lipid Homeostasis.
B. Studies of Caveolin-2-Deficient Mice
1. Relationship with Caveolin-1.
2. The Surprising Role of Caveolin-2 in the Lung.
C. Studies of Caveolin-3-Deficient Mice
1. Caveolin-3 and Muscle Disease.
2. Caveolin-3 and Transverse Tubules.
3. Caveolin-3 and the Dystrophin-Glycoprotein
Complex.
D. Dominant-Negative Caveolin Mutations in Human Disease
VII. Conclusions and Future Directions
A. Caveolae and Caveolins
B. Modifiers of Raft Function
Acknowledgments
References
Among the membrane compartments of a cell, vesicles known as
"caveolae" have long defied functional characterization. However, since the identification of a family of proteins termed
"caveolins", that form and reside in caveolae, a better
understanding has emerged. It is now clear that caveolae do not merely
play a singular role in the cell, but are pleiotropic in
nature
serving to modulate many cellular functions. The purpose of
this review is to explicate what is known about caveolins/caveolae and
highlight growing areas of caveolar research.
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X. Cheng and J. H. Jaggar Genetic ablation of caveolin-1 modifies Ca2+ spark coupling in murine arterial smooth muscle cells Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2309 - H2319. [Abstract] [Full Text] [PDF]
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 E. Sbaa, J. DeWever, P. Martinive, C. Bouzin, F. Frerart, J.-L. Balligand, C. Dessy, and O. Feron Caveolin Plays a Central Role in Endothelial Progenitor Cell Mobilization and Homing in SDF-1-Driven Postischemic Vasculogenesis Circ. Res., May 12, 2006; 98(9): 1219 - 1227. [Abstract] [Full Text] [PDF]
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V. A. Torres, J. C. Tapia, D. A. Rodriguez, M. Parraga, P. Lisboa, M. Montoya, L. Leyton, and A. F. G. Quest Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin J. Cell Sci., May 1, 2006; 119(9): 1812 - 1823. [Abstract] [Full Text] [PDF]
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N. Ullrich, A. Caplanusi, B. Brone, D. Hermans, E. Lariviere, B. Nilius, W. Van Driessche, and J. Eggermont Stimulation by caveolin-1 of the hypotonicity-induced release of taurine and ATP at basolateral, but not apical, membrane of Caco-2 cells Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1287 - C1296. [Abstract] [Full Text] [PDF]
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C. Schwencke, R. C. Braun-Dullaeus, C. Wunderlich, and R. H. Strasser Caveolae and caveolin in transmembrane signaling: Implications for human disease Cardiovasc Res, April 1, 2006; 70(1): 42 - 49. [Abstract] [Full Text] [PDF]
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R. C. Mora, V. L. Bonilha, B.-C. Shin, J. Hu, L. Cohen-Gould, D. Bok, and E. Rodriguez-Boulan Bipolar assembly of caveolae in retinal pigment epithelium Am J Physiol Cell Physiol, March 1, 2006; 290(3): C832 - C843. [Abstract] [Full Text] [PDF]
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S. Calaghan and E. White Caveolae modulate excitation-contraction coupling and {beta}2-adrenergic signalling in adult rat ventricular myocytes Cardiovasc Res, March 1, 2006; 69(4): 816 - 824. [Abstract] [Full Text] [PDF]
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A. F. El-Yazbi, W. J. Cho, G. Boddy, R. Schulz, and E. E. Daniel Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G394 - G403. [Abstract] [Full Text] [PDF]
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D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
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F. Sotgia, T. M. Williams, W. Schubert, F. Medina, C. Minetti, R. G. Pestell, and M. P. Lisanti Caveolin-1 Deficiency (-/-) Conveys Premalignant Alterations in Mammary Epithelia, with Abnormal Lumen Formation, Growth Factor Independence, and Cell Invasiveness Am. J. Pathol., January 1, 2006; 168(1): 292 - 309. [Abstract] [Full Text] [PDF]
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N. M. Urs, K. T. Jones, P. D. Salo, J. E. Severin, J. Trejo, and H. Radhakrishna A requirement for membrane cholesterol in the {beta}-arrestin- and clathrin-dependent endocytosis of LPA1 lysophosphatidic acid receptors J. Cell Sci., November 15, 2005; 118(22): 5291 - 5304. [Abstract] [Full Text] [PDF]
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C. Schwencke, A. Schmeisser, C. Walter, R. Wachter, S. Pannach, B. Weck, R. C. Braun-Dullaeus, M. Kasper, and R. H. Strasser Decreased caveolin-1 in atheroma: Loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis Cardiovasc Res, October 1, 2005; 68(1): 128 - 135. [Abstract] [Full Text] [PDF]
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K. Ohnuma, T. Yamochi, M. Uchiyama, K. Nishibashi, S. Iwata, O. Hosono, H. Kawasaki, H. Tanaka, N. H. Dang, and C. Morimoto CD26 Mediates Dissociation of Tollip and IRAK-1 from Caveolin-1 and Induces Upregulation of CD86 on Antigen-Presenting Cells Mol. Cell. Biol., September 1, 2005; 25(17): 7743 - 7757. [Abstract] [Full Text] [PDF]
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 P. Ratajczak, P. Oliviero, F. Marotte, F. Kolar, B. Ostadal, and J.-L. Samuel Expression and localization of caveolins during postnatal development in rat heart: implication of thyroid hormone J Appl Physiol, July 1, 2005; 99(1): 244 - 251. [Abstract] [Full Text] [PDF]
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W. G. Hill, E. Almasri, W. G. Ruiz, G. Apodaca, and M. L. Zeidel Water and solute permeability of rat lung caveolae: high permeabilities explained by acyl chain unsaturation Am J Physiol Cell Physiol, July 1, 2005; 289(1): C33 - C41. [Abstract] [Full Text] [PDF]
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A. M. Brainard, A. J. Miller, J. R. Martens, and S. K. England Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K+ current Am J Physiol Cell Physiol, July 1, 2005; 289(1): C49 - C57. [Abstract] [Full Text] [PDF]
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 N. E. Vlahakis and R. D. Hubmayr Cellular Stress Failure in Ventilator-injured Lungs Am. J. Respir. Crit. Care Med., June 15, 2005; 171(12): 1328 - 1342. [Abstract] [Full Text] [PDF]
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B. Ait-Mamar, M. Cailleret, C. Rucker-Martin, A. Bouabdallah, G. Candiani, C. Adamy, P. Duvaldestin, F. Pecker, N. Defer, and C. Pavoine The Cytosolic Phospholipase A2 Pathway, a Safeguard of {beta}2-Adrenergic Cardiac Effects in Rat J. Biol. Chem., May 13, 2005; 280(19): 18881 - 18890. [Abstract] [Full Text] [PDF]
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W. E. Schutzer, J. F. Reed, and S. L. Mader Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2457 - H2464. [Abstract] [Full Text] [PDF]
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P. H. Ratz, K. M. Berg, N. H. Urban, and A. S. Miner Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus Am J Physiol Cell Physiol, April 1, 2005; 288(4): C769 - C783. [Abstract] [Full Text] [PDF]
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A. D'Alessio, R. S. Al-Lamki, J. R. Bradley, and J. S. Pober Caveolae Participate in Tumor Necrosis Factor Receptor 1 Signaling and Internalization in a Human Endothelial Cell Line Am. J. Pathol., April 1, 2005; 166(4): 1273 - 1282. [Abstract] [Full Text] [PDF]
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X.-L. Wang, D. Ye, T. E. Peterson, S. Cao, V. H. Shah, Z. S. Katusic, G. C. Sieck, and H.-C. Lee Caveolae Targeting and Regulation of Large Conductance Ca2+-activated K+ Channels in Vascular Endothelial Cells J. Biol. Chem., March 25, 2005; 280(12): 11656 - 11664. [Abstract] [Full Text] [PDF]
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S. Ikeda, M. Ushio-Fukai, L. Zuo, T. Tojo, S. Dikalov, N. A. Patrushev, and R. W. Alexander Novel Role of ARF6 in Vascular Endothelial Growth Factor-Induced Signaling and Angiogenesis Circ. Res., March 4, 2005; 96(4): 467 - 475. [Abstract] [Full Text] [PDF]
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 A. W. Cohen, W. Schubert, D. L. Brasaemle, P. E. Scherer, and M. P. Lisanti Caveolin-1 Expression Is Essential for Proper Nonshivering Thermogenesis in Brown Adipose Tissue Diabetes, March 1, 2005; 54(3): 679 - 686. [Abstract] [Full Text] [PDF]
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T. M. Williams and M. P. Lisanti Caveolin-1 in oncogenic transformation, cancer, and metastasis Am J Physiol Cell Physiol, March 1, 2005; 288(3): C494 - C506. [Abstract] [Full Text] [PDF]
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R. S Ostrom Caveolins muscle their way into the regulation of cell differentiation, development, and function. Focus on "Muscle-specific interaction of caveolin isoforms: differential complex formation between caveolins in fibroblastic vs. muscle cells." Am J Physiol Cell Physiol, March 1, 2005; 288(3): C507 - C509. [Full Text] [PDF]
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P. Konig, J. Dedio, S. Oess, T. Papadakis, A. Fischer, W. Muller-Esterl, and W. Kummer NOSIP and Its Interacting Protein, eNOS, in the Rat Trachea and Lung J. Histochem. Cytochem., February 1, 2005; 53(2): 155 - 164. [Abstract] [Full Text] [PDF]
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R. Hnasko and N. Ben-Jonathan Developmental regulation of PV-1 in rat lung: association with the nuclear envelope and limited colocalization with Cav-1 Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L275 - L284. [Abstract] [Full Text] [PDF]
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A. Ost, U. Ortegren, J. Gustavsson, F. H. Nystrom, and P. Stralfors Triacylglycerol Is Synthesized in a Specific Subclass of Caveolae in Primary Adipocytes J. Biol. Chem., January 7, 2005; 280(1): 5 - 8. [Abstract] [Full Text] [PDF]
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L. J. Sampson, Y. Hayabuchi, N. B. Standen, and C. Dart Caveolae Localize Protein Kinase A Signaling to Arterial ATP-Sensitive Potassium Channels Circ. Res., November 12, 2004; 95(10): 1012 - 1018. [Abstract] [Full Text] [PDF]
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 J. Troost, H. Lindenmaier, W. E. Haefeli, and J. Weiss Modulation of Cellular Cholesterol Alters P-Glycoprotein Activity in Multidrug-Resistant Cells Mol. Pharmacol., November 1, 2004; 66(5): 1332 - 1339. [Abstract] [Full Text] [PDF]
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 J. K. Bendall, T. Damy, P. Ratajczak, X. Loyer, V. Monceau, I. Marty, P. Milliez, E. Robidel, F. Marotte, J.-L. Samuel, et al. Role of Myocardial Neuronal Nitric Oxide Synthase-Derived Nitric Oxide in {beta}-Adrenergic Hyporesponsiveness After Myocardial Infarction-Induced Heart Failure in Rat Circulation, October 19, 2004; 110(16): 2368 - 2375. [Abstract] [Full Text] [PDF]
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