The Proteasome is Involved in the Degradation of Different Aquaporin-2 Mutants Causing Nephrogenic Diabetes Insipidus
|Title:||The Proteasome is Involved in the Degradation of Different Aquaporin-2 Mutants Causing Nephrogenic Diabetes Insipidus|
|Authors:||Hirano, Kiyoko; Zuber, Christian; Roth, MD, PhD, Jurgen; Ziak, Martin|
|Publisher:||American Journal of Pathology|
|Date Published:||July 01, 2003|
You may, however, read this article at the American Journal of Pathology website.
To return to this page, use your "back" key.
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)
The researchers found that both the mutant and the normal AQP2 were formed in a part of the cell called the endoplasmic reticulum (ER). Proteins are measured in units of mass known as kilodaltons (kd). When the AQP2s under study are formed in their nonglycosylated forms (i.e., the form that does not have a linkage with a glycosyl group), they are slightly smaller than when they are synthesized in their glycosylated forms.
The mutants were dismantled by the cell much sooner than the normal AQP2. The nonglycosylated form of T126M was broken down by the cell over twice as quickly as the glycosylated form of T126M. The E258K AQP2 also was broken down by the cell far more quickly than the normal AQP2. However, where T126M was broken down by the enzyme, proteasome, E258K was broken down by both proteasome and lysosome. The E258K was directed to the lysosomes which disassembled it via an intracellular structure known as the Golgi apparatus, where it previously had been retained. T126M is retained in the ER. Both the ER and the Golgi apparatus function as a type of quality control center within the cell, holding misshapen proteins and either dismantling them or sending them elsewhere to be dismantled.
Though there were differences in how fast and where the two mutants were degraded, both were degraded by the cell. These differences could bear relevance to NDI research. For example, if researchers want to try and rescue the T126M from the ER and bring it to the cell surface, they should target the glycosylated form because it lasts longer. Also, since only proteasome seems to be involved in T126M, proteasome inhibitors might stabilize it and inhibit its dismantling by the cell.