Cloning, Characterization, and Chromosomal Mapping of Human Aquaporin of Collecting Duct
|Title:||Cloning, Characterization, and Chromosomal Mapping of Human Aquaporin of Collecting Duct|
|Authors:||Sasaki, Sei; Fushimi, MD, Kiyohide; Saito, Hidehiko; Saito, Fumiko; Uchida, Shinichi; Ishibashi, Kenichi; Kuwahara, Michio; Ikeuchi, Tatsuro; Inui, Ken-ichi; Nakajima, Kiichird; Watanabe, Tohru; Marumo, MD, Fumiaki|
|Publisher:||Journal of Clinical Investigation|
|Date Published:||March 01, 1994|
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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)
Normally, the apical membrane does not let much water permeate through it. But when the AQP is inserted into it, the apical membrane becomes extremely water permeable. Because of this, the kidney can reabsorb the body water flowing through the kidney CD. What liquid is left behind is the concentrated urine that is later voided.
Sasaki, et al., had recently cloned the cDNA of a water channel protein located in the CD of rat kidney (later, it was named aquaporin-2, AQP2). This protein was an important part of the rat's urine concentrating process. Sasaki, et al., sought to see if there was a protein similar in structure, size, function and location in the human kidney CD.
They succeeded in isolating a cDNA clone, which they called the human aquaporin of collecting duct (hAQP-CD -- later, hAQP2). The hAQP-CD was a 271-amino acid protein that was 91% similar to the rat AQP-CD (rAQP-CD), which was also a 271-amino acid protein. Like rAQP-CD, hAQP-CD was found only in the CD, located primarily in the apical and subapical areas of the CD principal cells. Again, like rAQP-CD, tests showed hAQP-CD increased the water permeability of laboratory cell culture and was inhibited by mercurial compounds. This indicated the hAQP-CD did function as a water channel. The authors were able to discover its chromosomal location: the q13 region of chromosome 12.
This knowledge might prove useful in the study of nephrogenic diabetes insipidus (NDI). NDI is a disorder characterized by the kidneys' inability to concentrate urine. Thus, the NDI patient experiences polyuria (chronic passage of large volumes of urine) and polydipsia (chronic, excessive thirst).
NDI can either be inherited or acquired. Recently, researchers discovered one cause of inherited NDI are mutations of the vasopressin-2 receptor gene. The authors, substantiating that hAQP-CD is the functional AQP responsible for increasing CD principal apical cell water permeability (thus allowing the kidney to concentrate urine), suggests it would be worth exploring if mutations in the hAQP-CD gene could be responsible for those cases of inherited NDI that are not caused by mutations in the V2R gene.