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
