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February 9, 2010
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Agre and Cells


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Aquaporins: Water Channels

The Nobel Prize Internet Archive



   10.08.03
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Two-thirds of our bodies consist of water. In this special ScienCentral News video, recently-named Nobel Prize winner Peter Agre explains the specially-designed cells that ensure we don't leak in the wrong places.

Watergates

This year's Nobel Prize in Chemistry is being shared by Peter Agre, a professor of biological chemistry and director of the graduate program in cellular and molecular medicine at Johns Hopkins University School of Medicine, for his discovery of water channels called aquaporins—a family of specialized proteins that sit in the membranes of cells and control the flow of water in and out. He shares the award with Roderick MacKinnon of The Rockefeller University in New York City.

"Our bodies are primarily made of water, about two-thirds of us are made of water," says Agre. "And that's true also of other species—mammals, fish, plants, bacteria. So the organization of water within our cells and tissues has to be very carefully orchestrated. The mechanisms by which water can cross cell membranes have been defined, and it's a subset of proteins that we refer to as aquaporins—the water pores." These proteins form narrow channels connecting the inside to the outside of cells. Only water, the smallest of biological molecules, is allowed to pass.





In 1991, Agre discovered aquaporin-1, the first molecular membrane water channel. "The humbling truth is the first aquaporin protein was discovered in our lab by simple accident. We were purifying the RH bloodgroup antigen from red cells, and we found another protein, similar in size, present in the kidney, related to some proteins in plants. But the function of none of these were known. And it was just the intuitive observation—'What could plants, kidneys, red blood cells share?'—that gave us the idea that maybe this is a fundamental process such as water transport."

frogcells
The frog egg cell on the right has been engineered to have aquaporins in its membrane.
image: Peter Agre
Agre first proved the existence of aquaporins in frog eggs. "We engineered frog eggs to express aquaporin proteins," Agre explains. "And when we put these frog eggs into fresh water, we found that unlike the normal frog eggs, which did not swell, the frog egg that had aquaporins in it swelled very rapidly and exploded—a remarkable difference, which immediately, upon the very first experiment, told the young people in the lab that this is, in fact, a molecular water channel. Rarely in our lab have we ever found a result so clear on the first try."




Aquaporins control how fluids like tears, sweat, urine, and even saliva move through our tissues. "The aroma of fresh cookies will immediately result in the secretion of large amounts of saliva," says Agre. "The movement of water through these glandular structures involves aquaporins."

Aquaporins are vital in regulating our body fluids, making sure our lungs stay moist and clean, the lenses in our eyes stay clear, and our kidneys continually filter waste and toxins from the bloodstream. "The normal function of our kidneys involves the filtration, the release of fluid, and the reabsorption of water and specific chemicals that we need," explains Agre. "In an average day, an average adult will have a release, a filtration of about 40 gallons of plasma, of which 99 percent will be reabsorbed. So the kidneys have this remarkable ability to reabsorb water, and this is entirely due to aquaporins."

Agre says that understanding aquaporins' role in human disease, and how to manipulate them, could prevent conditions like heat stroke, edema following stroke or head injury, and kidney failure. "In addition to the problems of brain swelling and kidney function and blindness, we think aquaporins will be involved in several other physiological events and disease states," says Agre. "The issue of body cooling during sweating, the barrier that our skin provides to infection, requires the presence of aquaporins—both for the prevention of infection and for the maximum healing of wounding. These are areas I think aquaporins will probably be involved clinically."

This research appeared in the July 2002 issue of the journal Physiology, and was funded by the National Institutes of Health and the Human Frontier Science Program Organization.


 
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