- News Home
6 March 2014 1:04 pm ,
Vol. 343 ,
Since 2000, U.S. government health research agencies have spent almost $1 billion on an effort to churn out thousands...
Magdalena Koziol, a former postdoc at Yale University, was the victim of scientific sabotage. Now, she is suing the...
Antiretroviral drugs can protect people from becoming infected by HIV. But so-called pre-exposure prophylaxis, or PrEP...
Two studies show that eating a diet low in protein and high in carbohydrates is linked to a longer, healthier life, and...
Considered an icon of conservation science, researchers at World Wildlife Fund (WWF) headquarters in Washington, D.C.,...
The new atlas, which shows the distribution of important trace metals and other substances, is the first product of...
Early in April, the first of a fleet of environmental monitoring satellites will lift off from Europe's spaceport in...
- 6 March 2014 1:04 pm , Vol. 343 , #6175
- About Us
Lockout Leads to Sex Reversal
16 December 2003 (All day)
SAN FRANCISCO, CALIFORNIA--Each year, a few babies are born with a male set of chromosomes and female genitalia. This sex reversal, called Swyer syndrome, can happen when a protein called SRY doesn't work. New research shows that in some cases, the altered protein has trouble entering the nucleus of fetal male gonadal cells. Thus, SRY can't turn on genes needed to make testes.
Getting certain proteins in and out of the nucleus is important for normal cellular functions. How important became clear this summer, when David Jans of Monash University in Victoria, Australia, Vincent Harley of Prince Henry's Institute of Medical Research in Victoria, Australia, and colleagues for the first time directly linked a defect in nuclear shuttling with a human syndrome. They reported that SRY molecules engineered to have the same changes found in some sex-reversed people, unlike normal SRY, seemed to have problems getting into the nucleus of cells.
A closer look revealed that a portion of the protein could no longer latch onto importin b, a factor that helps certain molecules slide into the nucleus. Most proteins use a sequence called a nuclear localization signal (NLS) to attract escort molecules. SRY has two NLS segments, and if the one that binds importin b is bungled, not enough SRY gets into the nucleus, they found.
In some sex-reversed people, however, the NLS recognized by importin b is normal, but the other NLS sequence is mutated. What this NLS recognizes was not well known, but it apparently interacts with a protein called calmodulin. Jans and colleagues modified the second NLS in SRY molecules in the same way that it is mutated in some sex-reversed people; the engineered protein failed to bind calmodulin. And when they repressed calmodulin activity in cells with normal SRY, they found that SRY could no longer easily enter the nucleus, Jans reported here this week at a meeting of the American Society for Cell Biology.
"It's important to understand SRY because it's the master trigger for maleness: With SRY one becomes a male, and without it one becomes a female," says geneticist Eric Vilain of the University of California, Los Angeles. The demonstration that a clinical syndrome can be caused by a molecule's inability to get into the nucleus is likely "just the tip of an iceberg" of diseases with similar mechanisms, says John Hanover, a cell biologist at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland.