Embedded within the membranes of our cells is a network of channels called aquaporins. These proteins act as highly selective gates, permitting only water molecules to pass into and out of the cell. The discovery of these water pores in 1992 by Peter Agre, earning him the 2003 Nobel Prize in Chemistry, revolutionized our understanding of cellular biology. Before this, scientists suspected that a specialized mechanism for water transport must exist, but its identity remained elusive. The identification of aquaporin-1 in red blood cells led to recognizing a large family of these channels, with at least 13 types now known in mammals.
The Structure of a Water Channel
An aquaporin’s ability to transport water at a rate of about three billion molecules per second while blocking other substances stems from its unique structure. The protein forms an hourglass shape within the cell membrane, creating a narrow channel that forces water molecules to pass in single file. This channel is composed of six alpha-helical domains that span the membrane, creating a barrel-like structure around a central pore. The protein exists as a tetramer, where four individual monomers cluster together, with each functioning as an independent water channel.
At the heart of its selectivity are two features. The narrowest point of the channel is a region known as the aromatic/arginine (ar/R) selectivity filter. This constriction is formed by a specific arrangement of amino acids that is just large enough for a water molecule but physically excludes larger solutes. Further into the channel lie two highly conserved loops containing a signature sequence of three amino acids: asparagine-proline-alanine (NPA). These NPA motifs create a unique electrostatic environment that reorients water molecules as they pass, breaking the hydrogen-bonded chains that would allow protons to sneak through.
Regulating Water Flow in the Body
In the human body, the regulation of water movement by aquaporins is fundamental to the function of numerous organ systems. The kidneys, in particular, rely heavily on these channels to manage the body’s water balance. At least seven different types of aquaporins are expressed in the kidneys. Aquaporin-1 (AQP1) is abundant in the proximal tubules, where it facilitates the bulk reabsorption of water from the initial filtrate back into the blood. In the collecting ducts, aquaporin-2 (AQP2) is controlled by the antidiuretic hormone vasopressin, allowing for the fine-tuning of water reabsorption to produce concentrated urine.
Red blood cells utilize aquaporins to withstand the mechanical stresses of circulation. As these cells travel through the body, they encounter varying osmotic pressures in different tissues. AQP1 channels in their membranes allow for rapid water movement, enabling the cells to swell or shrink quickly in response to these changes without rupturing.
The brain and eyes also depend on the controlled movement of water facilitated by aquaporins. In the brain, AQP4 is the most predominant type and regulates the movement of water between blood vessels and brain tissue, as well as the flow of cerebrospinal fluid. This helps maintain the brain’s fluid balance and clear waste products. In the eye, aquaporins, including AQP0 in the lens, are necessary for maintaining the transparency of the lens and the cornea, ensuring that light can pass through unimpeded to the retina.
Aquaporins and Health Conditions
When the function of aquaporins is disrupted, it can lead to significant health problems. The link between these channels and disease is illustrated by specific genetic conditions that affect water balance. One example is nephrogenic diabetes insipidus (NDI), a rare disorder characterized by the kidneys’ inability to concentrate urine, leading to excessive thirst and the production of large volumes of dilute urine. This condition is often caused by mutations in the gene for AQP2. These mutations can prevent the AQP2 protein from being correctly transported to the cell membrane, meaning the kidney cannot respond to hormonal signals to reabsorb water.
Problems with aquaporins can also affect vision. Congenital cataracts, a clouding of the eye’s lens present from birth, have been linked to mutations in the gene for AQP0. AQP0 is the major protein in the lens fiber cells, and besides transporting water, it is also thought to play a role in cell-to-cell adhesion. Mutations can disrupt the delicate water balance within the lens or interfere with its structural integrity, leading to the formation of opaque areas that scatter light and impair vision.
Beyond Humans
The importance of aquaporins extends far beyond the human body, as these channels are found in virtually all forms of life, from microbes to plants. In plants, aquaporins are fundamental for survival. They play a central role in water uptake from the soil by the roots and its transport to the leaves for photosynthesis. Regulating these channels is a mechanism for how plants respond to environmental stresses like drought and high salinity.
Even single-celled organisms such as bacteria rely on aquaporins to manage their internal hydration. While they may have fewer types of aquaporins compared to plants or mammals, these channels are still important for helping microbes adapt to changes in their environment by controlling the rapid movement of water across their cell membranes.