Water Transport Across Mammalian Cell Membranes
| Title: | Water Transport Across Mammalian Cell Membranes |
|---|---|
| Authors: | Verkman, Alan S.; Van Hoek, Alfred N.; Ma, Tonghui; Frigeri, Antonio; Skach, M.D., William R.; Mitra, Alok; Tamarappoo, B.K.; Farinas, Javier |
| Publisher: | American Journal of Physiology |
| Date Published: | January 01, 1996 |
| Reference Number: | 37 |
This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
In their review, the authors discuss the biophysics of water transport. They investigate whether parameters such as the permeability coefficient, activation energy, the ratio of osmotic-to-diffusional water permeability of the cell membrane, and solute selectivity of the water pathway through the cells could describe the geometric nature of the way water is transported across cells and the existence of water channels in cell membranes. Theoretically, a membrane with a high permeability coefficient, a low activation energy and a ratio of osmotic-to-diffusional water permeability greater than one should contain water-transporting proteins. They note, however, that these parameters are not always reliable.
The authors detail existing water permeability measurement methods and provide an overview of the aquaporin family members. However, this lay translation will focus on that portion of Verkman, et al., specific to the aquaporin that can be directly associated with nephrogenic diabetes insipidus (NDI): aquaporin-2 (AQP2).
AQP2 is found in the kidney collecting duct membrane. Its activity is determined by the antidiuretic hormone, vasopressin (AVP). When AVP binds with the vasopressin-2 receptor (V2R) it sets off a cascade of events that results in the kidneys maintaining water balance by reabsorbing water and concentrating urine. The part AQP2s play in this cascade is to, when signaled, shuttle to the top of the kidney collecting duct cells, insert themselves in the cell membrane in order to make them more water permeable so more water can flow through the cells and the urine can then be concentrated. After they perform their functions they shuttle back out of the cell membrane.
Mutations in AQP2 are associated with an extremely rare non-X-linked form of congenital NDI. At present it is unclear whether mutations in AQP2 make it nonfunctional in terms of allowing water passage, or whether they leave it functional but interfere with its ability to travel to the cell membrane where it is supposed to do its job.
Oddly enough, it is the mutated AQP2 that provides evidence that AQP2 does provide the physiological function of serving as a water channel for the kidney collecting duct cells. For when they are mutated, the all important water reabsorption and urine concentrating process does not take place. This results in the excessive urination characteristic of NDI. So far, AQP2 is the only known water channel whose function as a water channel which makes cell membranes more permeable to water has been proven.