The Ins and Outs of Aquaporin-2 Trafficking
|Title:||The Ins and Outs of Aquaporin-2 Trafficking|
|Publisher:||American Journal of Physiology: Renal Physiology|
|Date Published:||May 01, 2003|
You may, however, read this article at the American Journal of Physiology: Renal Physiology website.
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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)
In people with NDI there is a breakdown in this sequence and the AQP2 is not able to get to the cell membrane, or in some cases, it is not able to perform its job if it can get there. However, the author, Dennis Brown, reviews recent research that indicates that there are other ways AQP2 can reach the cell membrane other than the classically understood AVP initiated molecular path. This information might one day be applicable to people with NDI as it could provide alternative ways to get AQP2 to the section of the cell membrane (the apical, as opposed to the basolateral, section) where it performs its work.
Recent research with laboratory cell cultures indicates:
- Elevation of cyclic guanosine monophosphate (cGMP), induced by specific hormones or drugs, leads to accumulation of AQP2 in cell membranes in the kidney collecting duct (though mostly in the portion of the duct called the outer medulla). Though it appears that the protein kinase G (PKG) can bind the required phosphate molecules to the necessary section of AQP2 in laboratory cell cultures, it is not yet known if it can do so in cells in the human body or if this PKA effect does or does not include PKA.
- The fluid inside the cell, not counting the nucleus, is called the cytoplasm. It has a supporting structure called the cytoskeleton. A protein called actin that is part of the cytoskeleton is responsible for contraction and relaxation of part of the cytoskeleton, and, when stimulated with AVP, plays a role in getting AQP2 to the cell membrane. Recent research indicates that by manipulating actin, AQP2 can get to the cell membrane without AVP stimulation.
- After AQP2 reaches the cell membrane and performs its function, it recycles back into the cell interior. It does so in part by gathering in sacs coated by the protein, clathrin. Researchers have found that this clathrin coated return to the cell interior can be inhibited by expressing a form of the protein dynamin in cell cultures. Inhibiting AQP2’s return to the cell interior could result in the accumulation of more AQP2 in the cell membrane.
- Researchers now know that in cell cultures, AQP2 can perform its trip to the exterior of the cell and back without needing hormonal stimulation to do so. It remains to be discovered if it can do this in its natural location in the body.
- AQP2 can insert itself into the basolateral as well as the apical sections of the cell, and the pathways it takes in doing either can be affected by creating conditions where the net flow of water in the cells flows outside the cell.
- Other proteins such as small GTPases and the SNARE proteins play a role in moving AQP2 to and from the cell membrane.
Brown observes that understanding the cAMP independent mechanisms for AQP2 transport to and from the cell membrane is important for NDI research because this could lead to ways of bypassing the normal route which is not fully available to people with NDI.