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AHA! MOMENTS
November 3, 2003

PETER C. AGRE

Nobel Laureate recognized protein "contaminant" as a water channel

AMANDA YARNELL, C&EN WASHINGTON

Photo by Amanda Yarnell
Peter C. Agre, a professor of medicine and biological chemistry at Johns Hopkins University School of Medicine, was awarded the 2003 Nobel Prize in Chemistry for discovering a class of membrane-spanning proteins that transport water across cell membranes. Called the aquaporins, these water channels are crucial for a variety of physiological processes in humans, including vision and water reabsorption in the kidneys. In plants, they control water uptake in the roots as well as water distribution to the stalk, leaves, and flowers. Although a few biophysicists had suggested that cells might have membrane channels specific for water, most scientists thought that water got in and out of cells by simple diffusion across the cell membrane. That changed in 1988, when Agre stumbled upon the first aquaporin while trying to purify another protein from red blood cells. Here he recalls that "Aha!" moment in his career:

"When we first identified this protein, ironically we thought it was a contaminant. A wiser scientist might have said, 'Well, just disregard the dirt and concentrate on the important stuff.' But we found that there is a lot of this contaminant protein in red blood cells, and we also found that it was very abundant in kidney cells [and in plant roots]. Yet no one studying red blood cells had ever found it, even though it turned out to be astonishingly abundant--there were nearly 200,000 copies per [red blood] cell. That's kind of like driving out to western Maryland and finding a town of 200,000 people that's not even on the map. It tends to get your attention.

EXPLOSIVE When placed in distilled water, frog eggs that contain aquaporin take in so much water that they explode. Frog eggs without the protein don't.
Illustration by Typoform

"So I asked myself, What do red blood cells, renal cells, and the roots of plants have in common? There aren't too many things. But the movement of water is one such thing. It was suggested to me by my mentor and dear friend, John Parker of the University of North Carolina, Chapel Hill, that I consider water transport.

"To test our hypothesis, we used Xenopus oocytes (frog eggs). We put one set of oocytes in saline buffer [as a control]. Into a second set of oocytes, we injected 2 nanograms of the RNA encoding this protein that we thought might be a water channel. After culturing these sets of eggs for a few days, we transferred them from the saline buffer solution into fresh water. After a few minutes, the control oocytes didn't change. They are water impermeable. But the oocytes [that contain the water channel protein] swelled up and imploded--really quite violently--like popcorn popping. That experiment changed life as we knew it in our lab."



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Chemisty Prize For Cell Channels
[C&EN, Oct. 13, 2003]
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