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Science 293 (5539): 2449-2452

Copyright © 2001 by the American Association for the Advancement of Science

Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice

Marek Drab,12 Paul Verkade,1 Marlies Elger,3 Michael Kasper,4 Matthias Lohn,23 Birgit Lauterbach,23 Jan Menne,3 Carsten Lindschau,23 Fanny Mende,1 Friedrich C. Luft,2 Andreas Schedl,5 Hermann Haller,3 Teymuras V. Kurzchalia1*

Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor suppression. By targeted disruption of caveolin-1, the main protein component of caveolae, we generated mice that lacked caveolae. The absence of this organelle impaired nitric oxide and calcium signaling in the cardiovascular system, causing aberrations in endothelium-dependent relaxation, contractility, and maintenance of myogenic tone. In addition, the lungs of knockout animals displayed thickening of alveolar septa caused by uncontrolled endothelial cell proliferation and fibrosis, resulting in severe physical limitations in caveolin-1-disrupted mice. Thus, caveolin-1 and caveolae play a fundamental role in organizing multiple signaling pathways in the cell.

1 Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauer-Strasse 108, D-01307 Dresden, Germany.
2 Franz Volhard Clinic and Max-Delbrück-Center for Molecular Medicine, Humboldt University Berlin, Wiltberg-Strasse 50, D-13125 Berlin, Germany.
3 Hannover Medical School, Karl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
4 Institute of Anatomy, Technical University of Dresden, Fetscher-Strasse 74, D-01307 Dresden, Germany.
5 Max-Delbrück-Center for Molecular Medicine, Robert-Roessle-Strasse 10, D-13125 Berlin, Germany.
*   To whom correspondence should be addressed. E-mail: kurzchalia{at}mpi-cbg.de



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Role of caveolin-1 in thyroid phenotype, cell homeostasis, and hormone synthesis: in vivo study of caveolin-1 knockout mice.
M. Senou, M. J. Costa, C. Massart, M. Thimmesch, C. Khalifa, S. Poncin, M. Boucquey, A.-C. Gerard, J.-N. Audinot, C. Dessy, et al. (2009)
Am J Physiol Endocrinol Metab 297, E438-E451
   Abstract »    Full Text »    PDF »
Unaltered size selectivity of the glomerular filtration barrier in caveolin-1 knockout mice.
G. Grande, C. Rippe, A. Rippe, A. Rahman, K. Sward, and B. Rippe (2009)
Am J Physiol Renal Physiol 297, F257-F262
   Abstract »    Full Text »    PDF »
Macrophage Sphingomyelin Synthase 2 Deficiency Decreases Atherosclerosis in Mice.
J. Liu, C. Huan, M. Chakraborty, H. Zhang, D. Lu, M.-S. Kuo, G. Cao, and X.-C. Jiang (2009)
Circ. Res. 105, 295-303
   Abstract »    Full Text »    PDF »
Vascular Caveolin Deficiency Supports the Angiogenic Effects of Nitrite, a Major End Product of Nitric Oxide Metabolism in Tumors.
F. Frerart, I. Lobysheva, B. Gallez, C. Dessy, and O. Feron (2009)
Mol. Cancer Res. 7, 1056-1063
   Abstract »    Full Text »    PDF »
MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.
M. Bastiani, L. Liu, M. M. Hill, M. P. Jedrychowski, S. J. Nixon, H. P. Lo, D. Abankwa, R. Luetterforst, M. Fernandez-Rojo, M. R. Breen, et al. (2009)
J. Cell Biol. 185, 1259-1273
   Abstract »    Full Text »    PDF »
Molecular mechanisms of clathrin-independent endocytosis.
C. G. Hansen and B. J. Nichols (2009)
J. Cell Sci. 122, 1713-1721
   Abstract »    Full Text »    PDF »
Binding of IFITM1 enhances the inhibiting effect of caveolin-1 on ERK activation.
Y. Xu, G. Yang, and G. Hu (2009)
Acta Biochim Biophys Sin 41, 488-494
   Abstract »    Full Text »    PDF »
Monomeric C-reactive protein activates endothelial cells via interaction with lipid raft microdomains.
S.-R. Ji, L. Ma, C.-J. Bai, J.-M. Shi, H.-Y. Li, L. A. Potempa, J. G. Filep, J. Zhao, and Y. Wu (2009)
FASEB J 23, 1806-1816
   Abstract »    Full Text »    PDF »
Akt-Mediated Transactivation of the S1P1 Receptor in Caveolin-Enriched Microdomains Regulates Endothelial Barrier Enhancement by Oxidized Phospholipids.
P. A. Singleton, S. Chatchavalvanich, P. Fu, J. Xing, A. A. Birukova, J. A. Fortune, A. M. Klibanov, J. G. N. Garcia, and K. G. Birukov (2009)
Circ. Res. 104, 978-986
   Abstract »    Full Text »    PDF »
eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues.
J.-L. Balligand, O. Feron, and C. Dessy (2009)
Physiol Rev 89, 481-534
   Abstract »    Full Text »    PDF »
The Heme Oxygenase-1/Carbon Monoxide Pathway Suppresses TLR4 Signaling by Regulating the Interaction of TLR4 with Caveolin-1.
X. M. Wang, H. P. Kim, K. Nakahira, S. W. Ryter, and A. M. K. Choi (2009)
J. Immunol. 182, 3809-3818
   Abstract »    Full Text »    PDF »
Caveolin-2 Is Required for Apical Lipid Trafficking and Suppresses Basolateral Recycling Defects in the Intestine of Caenorhabditis elegans.
S. Parker, D. S. Walker, S. Ly, and H. A. Baylis (2009)
Mol. Biol. Cell 20, 1763-1771
   Abstract »    Full Text »    PDF »
Enhanced myogenic constriction of mesenteric artery in heart failure relates to decreased smooth muscle cell caveolae numbers and altered AT1- and epidermal growth factor-receptor function.
Y. Xu, R. H. Henning, M. Sandovici, J. J. van der Want, W. H. van Gilst, and H. Buikema (2009)
Eur J Heart Fail 11, 246-255
   Abstract »    Full Text »    PDF »
Dysfunctional Microvasculature as a Consequence of Shb Gene Inactivation Causes Impaired Tumor Growth.
N. S. Funa, V. Kriz, G. Zang, G. Calounova, B. Akerblom, J. Mares, E. Larsson, Y. Sun, C. Betsholtz, and M. Welsh (2009)
Cancer Res. 69, 2141-2148
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Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity.
P. M. Haram, O. J. Kemi, S. J. Lee, M. O. Bendheim, Q. Y. Al-Share, H. L. Waldum, L. J. Gilligan, L. G. Koch, S. L. Britton, S. M. Najjar, et al. (2009)
Cardiovasc Res 81, 723-732
   Abstract »    Full Text »    PDF »
Cell Entry of Arginine-rich Peptides Is Independent of Endocytosis.
G. Ter-Avetisyan, G. Tunnemann, D. Nowak, M. Nitschke, A. Herrmann, M. Drab, and M. C. Cardoso (2009)
J. Biol. Chem. 284, 3370-3378
   Abstract »    Full Text »    PDF »

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