"...it's a whole system that we didn't realize existed."
Exploiting what appears to be a newly found regulator of cystic fibrosis chemistry, scientists at Johns Hopkins report they have been able to experimentally improve the function of the cell molecule most affected by this common inherited disorder.
Writing in the October edition of the journal Cell, the Hopkins team described their discovery of a previously unknown system that helps control the protein product made by the cystic fibrosis gene, called CFTR.
CFTR protein molecules shape themselves into channels in the cells that line the lungs and other organ targets of cystic fibrosis, the most common lethal genetic disease in Caucasians. Cystic fibrosis is a recessive disorder marked by accumulation of mucus and by abnormal sweat, digestive and other secretory glands.
At the biochemical level, the channels are a main way cells regulate the flow of salts in and out of cells. "People with cystic fibrosis have abnormal chemistry outside of cells, not because their CFTR molecules won't work, but largely because they have too few of them on their cell membranes," says molecular biologist Min Li, Ph.D., who led the research team.
In the Hopkins study done on human tissues, human and mouse cell cultures and isolated cell membranes, Li and his team showed that a regulatory cell protein called CAP 70 lies adjacent to CFTR in cell membranes and binds to CFTR as well. Moreover, when CAP 70, also a protein, is present, it links two CFTR molecules together, subtly changing the shape of each so they work together more efficiently. "This counters the decades-old idea that CFTR exists only as single molecules," says Li. "There's a whole control system here we didn't know existed before."
Potentially, what this means is that in CF patients, existing channels could be made to work more efficiently. "We might be able to compensate for their having too few of them," says Li. In on
Contact: Marjorie Centofanti
Johns Hopkins Medical Institutions