Durham, NC?Aquaporins are the water channel proteins, the body's plumbing system, that move water across the biological compartments and without which life would cease, according to Peter Agre, MD.
Durham, NC-Aquaporins are the water channel proteins, the body's plumbing system, that move water across the biological compartments and without which life would cease, according to Peter Agre, MD.
"A fundamental problem in the biology of water is the movement of water across biological compartments. In the eye, this includes tear secretion and reuptake of aqueous humor. In the rest of the body, these functions include secretion of sweat, the concentration of urine, and release of bile, for example. All of these processes involve movement of water across biological barriers," said Dr. Agre, who delivered one of the keynote addresses at the annual meeting of the Association for Research in Vision and Ophthalmology last year in Fort Lauderdale, FL. The aquaporins facilitate these bodily functions through transmembrane water permeability.
Bilayer diffusion, he explained, is insufficient to explain the rapid water movement in vision. Early researchers in this field believed that there were selective high-capacity channels permeated by water (H2O) that were not permeated by protons, which exist as a hydronium ion (H3O+ ).
For example, to make 1 l of urine, the human kidneys filter about 180 l of plasma per day and reabsorb about 99% of the water. On the one hand, without reabsorption of water one would die of dehydration, but if one reabsorbs the water with protons, systemic acidosis would result, he explained.
The water channel molecules are neutral pores that let the neutral water molecules rapidly cross biologic membranes through osmosis.
A seminal observation occurred in the 1970s in this area when Robert Macey at the University of California Berkeley discovered that mercuric chloride inhibited water permeability while measuring water transport in red blood cell membranes. Conversely, when the membranes were treated with a reducing agent, the water permeability was restored. His hypothesis was that water transport occurred through proteinaceous pores with a free sulfhydryl group. Despite this, belief in the presence of anything other than diffusion was viewed with skepticism.
When Dr. Agre, who is a hematologist, and colleagues were working on the Rh blood group antigens, which they successfully isolated, they found these proteins to be abundant in cells. They also identified a previously unknown and unrelated protein of similar size. This new protein, now referred to as AQP1, is present in red cells and kidney tubules, and related proteins are found throughout nature, including plants. They recognized that red cells, kidney tubular epithelial cells, and plant cells all could move water rapidly. They tested the function of AQP1 by expressing complementary RNA in frog oocytes. When placed in distilled water, the control oocytes did not swell; however, the oocytes expressing AQP1 swelled rapidly and exploded.
Dr. Agre and colleagues then concentrated efforts on studying the structure of the molecule. They found ultimately that when cysteine 189 in the molecule is replaced by a serine, it supports the transport of water, he explained, but is not inhibited by mercury. Two loops in this molecule form a single aqueous pore through each subunit, they theorized, forming a structure that they term the "hourglass." This was confirmed and refined by worldwide collaborations.
Aquaporins in the eye
Aquaporin is distributed in the lens epithelium, the corneal endothelium, nonpigmented epithelium (ciliary and iris), and the trabecular meshwork. Other members of the aquaporin family have also been identified-aquaporin-3 (conjunctiva), aquaporin-4 (perivascular membranes in glial cells, Müller cells), and aquaporin-5 (corneal epithelium and lacrimal glands), Dr. Agre explained.
Aquaporins are involved in numerous diseases, according to Dr. Agre.
"The first challenge in understanding the physiology and pathophysiology of aquaporins is knowing exactly where the proteins are expressed at the cellular and subcellular level," he stated.
Early work on kidneys by collaborators showed that aquaporin-1 was abundant throughout the organ but not in the collecting ducts. The protein is scarce in the cell body but present at the apical surface where water is absorbed.