دورية أكاديمية
Functionality of aquaporin-2 missense mutants in recessive nephrogenic diabetes insipidus.
| العنوان: | Functionality of aquaporin-2 missense mutants in recessive nephrogenic diabetes insipidus. |
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| المؤلفون: | Marr N; Department of Cell Physiology, Medical Center of the University of Nijmegen, Nijmegen, The Netherlands., Kamsteeg EJ, van Raak M, van Os CH, Deen PM |
| المصدر: | Pflugers Archiv : European journal of physiology [Pflugers Arch] 2001 Apr; Vol. 442 (1), pp. 73-7. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: Germany NLM ID: 0154720 Publication Model: Print Cited Medium: Print ISSN: 0031-6768 (Print) Linking ISSN: 00316768 NLM ISO Abbreviation: Pflugers Arch Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin, New York, Springer. |
| مواضيع طبية MeSH: | Mutation, Missense*, Aquaporins/*genetics , Aquaporins/*physiology , Diabetes Insipidus, Nephrogenic/*genetics, Amino Acid Sequence ; Animals ; Aquaporin 2 ; Aquaporin 6 ; Aquaporins/chemistry ; Cell Membrane/metabolism ; Cell Membrane Permeability ; Diabetes Insipidus, Nephrogenic/physiopathology ; Endoplasmic Reticulum/metabolism ; Female ; Gene Expression ; Glycosylation ; Immunoblotting ; Mannose/metabolism ; Molecular Sequence Data ; Oocytes/metabolism ; Osmosis ; Transfection ; Water/metabolism ; Xenopus laevis |
| مستخلص: | Aquaporin-2 (AQP2) missense mutants in recessive nephrogenic diabetes insipidus (NDI) are all retained in the endoplasmic reticulum (ER), but some could function as water channels. No conclusions could be drawn about the water permeability (Pf) of others, because there was no method for quantifying AQP2 expression in the plasma membrane. We recently developed such a method, which has allowed us to study the functionality of these AQP2 mutants. Immunoblot analysis of membranes of injected oocytes revealed that all mutants (AQP2-G64R, AQP2-N68S, AQP2 T126M, AQP2-A147T, AQP2-R187C, AQP2-S216P) are expressed as unglycosylated and high-mannose glycosylated AQP2. The level of the high-mannose form of AQP2-A147T in the plasma membranes was low, indicating that this mutation has a less severe effect on proper folding. Analysis of Pf values and plasma membrane expression levels reveals that AQP2-N68S, AQP2-R187C and AQP2-S216P are non-functional, AQP2-A147T is as functional as wt-AQP2, while AQP2-T126M and AQP2-G64R retain 20% of the permeability of wt-AQP2. Since G64 is highly conserved between AQPs and expected to form essential interactions with other amino acids within AQP1, the residual functionality of AQP2-G64R is surprising. Our data furthermore indicate that an eventual therapy with chemical chaperones that restores the routing of AQP2 mutants to the apical membrane of collecting ducts cells might relieve NDI in patients encoding AQP2-A147T, and to a lesser extent AQP2-T126M and AQP2-G64R, but not in patients encoding AQP2-N68S, AQP2-R187C or AQP2-S216P. |
| المشرفين على المادة: | 0 (Aquaporin 2) 0 (Aquaporin 6) 0 (Aquaporins) 059QF0KO0R (Water) PHA4727WTP (Mannose) |
| تواريخ الأحداث: | Date Created: 20010526 Date Completed: 20011101 Latest Revision: 20131121 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1007/s004240000498 |
| PMID: | 11374071 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0031-6768 |
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| DOI: | 10.1007/s004240000498 |