Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice.
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.
Drab
M
M
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauer-Strasse 108, D-01307 Dresden, Germany.
Verkade
P
P
Elger
M
M
Kasper
M
M
Lohn
M
M
Lauterbach
B
B
Menne
J
J
Lindschau
C
C
Mende
F
F
Luft
F C
FC
Schedl
A
A
Haller
H
H
Kurzchalia
T V
TV
D000418:Albumins / Q000134:cerebrospinal fluid; D000818:Animals; D001011:Aorta / Q000502:physiology* / Q000648:ultrastructure; D001247:Asthenia / Q000209:etiology; D020013:Calcium Signaling; D021941:Caveolae / Q000502:physiology* / Q000648:ultrastructure; D051242:Caveolin 1; D022461:Caveolins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D018390:Gene Targeting; D066298:In Vitro Techniques; D008055:Lipids / Q000032:analysis; D008168:Lung / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000737:chemistry / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000209:etiology; D015398:Signal Transduction
D000418:Albumins; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D008055:Lipids; D009569:Nitric Oxide; D002784:Cholesterol