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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.
"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."
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."