Knockout of cav-1 protein causes loss of a cellular organelle

August 10, 2001

Scientists from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, the Franz Volhard Clinic of the Charité, Humboldt-University Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, were able to cause loss of caveolae and by studying mice lacking this organelle, describe the function of caveolae in mammals. The latest issue of the scientific journal "Science" (published online August 9, 2001; 10.1126/science. 1062688 (Science Express Reports)) reports the current status of the research "Loss of caveolae, vascular dysfunction and pulmonary defects in caveolin-1 gene-disrupted mice".

An exciting new discovery and possibly providing the first example of an organelle knockout is the absence of caveolae after the protein caveolin-1 (cav-1) is genetically prevented from being expressed in transgenic mice. The scientists have characterised the phenotype of transgenic mice that lack caveolin-1 and have found that the mice lack caveolae, the small cave-like invaginations of the plasma membrane of a variety of eukaryotic cells. More than 50 years after the discovery of caveolae their function remains a matter of speculation and controversy. The study provides clues as to the function of these organelles and also provides the first example of the effect of removing a cellular organelle.

Caveolae have been associated with various cellular processes such as transcytosis of solutes through endothelial cells, cholesterol transport, signal transduction and tumor suppression. They have a characteristic flask-shape with a diameter of 50-100 nm and are present on many cell types, including endothelial, smooth muscle cells and fat cells. They represent a form of lipid rafts within the plasma membrane, enriched in cholesterol and glycolipids. Cav-1, a small protein of only 21-22 kDa, is to date the best biochemical marker for caveolae. It is assumed to be the major structural component of the caveolar coat that is seen in electron micrographs.

By targeted disruption of caveolin-1, the main protein component of caveolae, Drs. Teymuras V. Kurzchalia and Marek Drab and their colleagues have generated mice that lack 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 mutant animals displayed dramatic thickening of alveolar septa caused by uncontrolled endothelial cell proliferation and fibrosis. These defects resulted in severe physical limitations in caveolin-1-disrupted mice but were not lethal. These data demonstrate a fundamental role of caveolin-1 and caveolae in organizing multiple signalling pathways in the cell and indicate important physiological roles for caveolae in lung function and the cardiovascular system.
-end-


Max-Planck-Gesellschaft

Related Genetics Articles from Brightsurf:

Human genetics: A look in the mirror
Genome Biology and Evolution's latest virtual issue highlights recent research published in the journal within the field of human genetics.

The genetics of blood: A global perspective
To better understand the properties of blood cells, an international team led by UdeM's Guillaume Lettre has been examining variations in the DNA of 746,667 people worldwide.

Turning to genetics to treat little hearts
Researchers makes a breakthrough in understanding the mechanisms of a common congenital heart disease.

New drugs more likely to be approved if backed up by genetics
A new drug candidate is more likely to be approved for use if it targets a gene known to be linked to the disease; a finding that can help pharmaceutical companies to focus their drug development efforts.

Mapping millet genetics
New DNA sequences will aid in the development of improved millet varieties

Genetics to feed the world
A study, published in Nature Genetics, demonstrated the effectiveness of the technology known as genomic selection in a wheat improvement program.

The genetics of cancer
A research team has identified a new circular RNA (ribonucleic acid) that increases tumor activity in soft tissue and connective tissue tumors.

New results on fungal genetics
An international team of researchers has found unusual genetic features in fungi of the order Trichosporonales.

Mouse genetics influences the microbiome more than environment
Genetics has a greater impact on the microbiome than maternal birth environment, at least in mice, according to a study published this week in Applied and Environmental Microbiology.

New insights into genetics of fly longevity
Alexey Moskalev, Ph.D., Head of the Laboratory of Molecular Radiobiology and Gerontology Institute of Biology, and co-authors from the Institute of biology of Komi Science Center of RAS, Engelgard's Institute of molecular biology, involved in the study of the aging mechanisms and longevity of model animals announce the publication of a scientific article titled: 'The Neuronal Overexpression of Gclc in Drosophila melanogaster Induces Life Extension With Longevity-Associated Transcriptomic Changes in the Thorax' in Frontiers in Genetics - a leading open science platform.

Read More: Genetics News and Genetics Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.