Mechanisms and Regulation of Water Transport in the Kidney
| Title: | Mechanisms and Regulation of Water Transport in the Kidney |
|---|---|
| Authors: | Harris, H. William; Zeidel, Mark L.; Strange, Kevin; Emma, MD, Francesco |
| Publisher: | Seminars in Nephrology |
| Date Published: | March 01, 1993 |
| Reference Number: | 272 |
N/A
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 membranes have a very low permeability. That is, they do not easily let water through them. (Current research indicates that the layers and distribution of fats (lipids) in the apical membrane are what makes it so water impermeable.) But when the WCs are inserted into the apical membranes, the membranes increase their degree of water permeability up to 100-fold. This increased water permeability allows the kidney to reabsorb the body water passing through the kidney collecting duct. What remains is concentrated urine that is later voided.
Water channels are a family of proteins that, when inserted into the cell membrane form a channel through which water can flow. (Some WCs only let water through; others allow small ions through as well.) Some WCs are found widely throughout the body, others have more limited locations. Some WCs are regulated by the presence or absence of a specific hormone; others function independently of hormonal stimulation. The WCs discussed in this paper primarily are those regulated by ADH.
In the absence of ADH, WCs reside inside little sacs called water channel vesicles (WCVs). The WCVs are located inside the cell. When signaled by the ADH-initiated molecular sequence, they travel to the apical membrane and fuse with it. This is when the WCs are inserted into the apical membrane. When ADH absents itself from the cell, the WCs are retrieved from the apical membrane in the following manner:
- The WCVs are taken up in pits that pock the cell membrane surface. (These pits may be coated with a protein called clathrin.)
- The coated pits are taken back within the cell. There they lose their coat (and are then called endosomes).
- The endosomes hold within them the WCVs.
A very similar process takes place in the granular cells of the toad urinary bladder. WCs reside in little sacs called aggrephores. When ADH binds to receptors on the cell surface, it induces the WC-containing aggrephores to travel to and fuse with the apical membrane of the granular cell. Then, the WCs are inserted and the apical membrane water permeability increases many-fold. When ADH absents itself, sections of the apical membrane containing WCs are retrieved from the apical membrane by vesicles.
The movement from the cell surface to its interior is called endocytosis. Researchers studying the endocytotic movement of WCVs in the toad bladder have defined three stages of the process. Immediately after retrieval from the apical membrane, WCs are found in vesicles beneath the apical membrane. Thirty minutes after the WCs are retrieved, they are found in multi-vesicular bodies (MVB). One hour after WC retrieval, no WCs can be found in the MVBs, and the acid content of the MVBs is higher than the previous vesicles. Further studies focusing on the functioning of WCs indicate that the early endosomes (vesicles) and the 30-minute MVBs contain functional WCs, but the 60-minute MVBs do not. Researchers suggest that WC are retrieved into subapical endosomes that initially cannot acidify and which help the WCs remain functional. Over the next one to two hours, the MVBs become acidic, perhaps enabling them to dissolve WCs or render them nonfunctional. It is, at present, unclear as to how many times, if at all, functional WCs can be recycled back to the apical membrane to be used to once again help increase its water permeability.
Though retrieval of WCVs from the apical membrane occurs when ADH absents itself from the cell, it is not clear if that is the only thing that signals WC retrieval. Currently researchers suspect that cell swelling or cytoplasmic dilution may also stimulate the retrieval.
Researchers suspect that G-proteins may be involved in signaling WCVs to move to the apical membrane. These proteins cycle between active and inactive states, acting as a molecular switch which may help them signal the WCVs. As to the mechanical events by which WCVs move to, fuse with, and are retrieved from the apical membrane, researchers suggest that microtubles within the cell might function as tracks on which the WCVs are moved to the apical membrane by such "molecular motors" as dynein or kinesin.
As of this article, researchers have been able to clone one member of the WC family, CHIP-28. This will enable researchers to determine the relationship between this WC's molecular structure and function. Similar cloning and research is being attempted on other WCs as well.