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© The Rockefeller University Press, 0021-9525/2001/9/904-a $5.00
The Journal of Cell Biology, Volume 154, Number 5, September 3, 2001 904-a-905

An organelle knockout

Swimming is a problem despite remaining lipid rafts. Kurzchalia/AAAS

By knocking out a single gene for caveolin-1, Teymuras Kurzchalia (Max Planck Institute, Dresden, Germany) and colleagues have ablated a special subset of lipid rafts called caveolae. The resulting mice survive, perhaps surprisingly, but show alterations in signaling that affect cell contractility and proliferation.

Caveolin-1 is the major protein in caveolae, and its oligomerization and cholesterol binding may help form these flask-shaped invaginations. Caveolae have been implicated in both transcytosis and signaling, but the knockout mice seem to retain functional transcytosis in endothelial cells that now lack caveolae. "In the beginning I thought transport through the endothelium would be totally destroyed," says Kurzchalia. "After almost 50 years, this hypothesis needs to be fundamentally revised."

Vasoconstriction and myogenic tone are dysregulated in the knockout mice, probably as a result of hyperactive endothelial nitric oxide synthase (eNOS). Kurzchalia suspects that caveolae function as a dumping ground for various signaling molecules, including eNOS, which arrive from other raft systems and are then inactivated upon arrival. Another substrate for this inhibition pathway is inducible NOS (iNOS). Its hyperactivation results in permanent erections for the unfortunate male knockout mice.

Dysregulation of other signaling pathways may explain the hyperproliferation and fibrosis seen in the lungs of the knockout mice, which leads to poor performance in swimming endurance tests. Kurzchalia hopes to identify the relevant signaling pathways by studying the proliferation of knockout cells in culture.

Reference:

Drab, M., et al. 2001. Science. 10.1126/science.1062688, http://www.sciencemag.org/cgi/content/abstract/1062688.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 142K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?