The Aquaporin Family of Molecular Water Channels
| Title: | The Aquaporin Family of Molecular Water Channels |
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| Author: | Knepper, Mark |
| Publisher: | Proceedings of the National Academy of Sciences of the U.S.A |
| Date Published: | July 05, 1994 |
| Reference Number: | 378 |
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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)
All aquaporins share a similar structure. They are all proteins, strings of amino acids. To visualize what they generally look like, imagine that a major portion of the string lies within a membrane in six coiled clumps called membrane domains 1 - 6. Part of the string snakes outside the cell forming three curves called extracellular loops A, C and E. Part of it snakes inside the cell, forming two curves called intracellular loops B and D. Both ends of the protein, the amino terminus and the carboxy terminus, lie inside the cell with the intracellular loops. (Please see AQP2 for a representation of an aquaporin.)
Some of the aquaporins will not function as water channels until signaled to do so by a hormone. Most aquaporins do not require hormonal signals to function. They are what is called constitutively placed in the membranes and function independently of hormones.
Of the aquaporins, aquaporin-2 (AQP2) bears the most relevance to nephrogenic diabetes insipidus (NDI). NDI is a disorder characterized by the kidney's inability to reabsorb body water flowing through the kidney collecting ducts (CDs). AQP2s are located in the CD principal cells. Regulated by the antidiuretic hormone, vasopressin (VP), AQP2s travel to and are inserted into the apical membrane of the CD principal cells when signaled to do so by VP. Once inserted, they allow much more water than usual to flow across the apical membrane. When VP absents itself from the cell, the AQP2s are retrieved from the membrane and it returns to its normal state of low water permeability where little water can cross its membrane. This shuttling back and forth of the AQP2 to the membrane is part of the process that allows the kidney to reabsorb the water flowing through the CD. The ability to do this is what allows the kidney to concentrate urine and balance body water.
There are two different genes that, when mutated, can cause NDI. One is the vasopressin-2 receptor gene, the gene that codes for the vasopressin-2 receptor (V2R), the receptor that VP binds with to initiate the urine concentrating process. The other is the AQP2 gene, which codes for the AQP2. If the AQP2s are mutated, then they cannot perform their function of making the apical membrane more water permeable, and the kidney is unable to reabsorb the body water flowing through the CD.