Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor
Publication year
2011Source
NDT Plus, 4, 3, (2011), pp. 158-163ISSN
Publication type
Article / Letter to editor
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Organization
Physiology
Journal title
NDT Plus
Volume
vol. 4
Issue
iss. 3
Page start
p. 158
Page end
p. 163
Subject
NCMLS 5: Membrane transport and intracellular motility IGMD 9: Renal disorderAbstract
Mutations in the arginine vasopressin receptor 2 (AVPR2) gene can cause X-linked nephrogenic diabetes insipidus (NDI) characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel mutation in the AVPR2 gene (L170P) located in the fourth transmembrane domain in a Danish NDI male. Analysis of the mutant receptor in Madin-Darby Canine Kidney cell culture revealed that AVPR2-L170P was retained in the endoplasmic reticulum, and the expression was dramatically downregulated compared to wild-type AVPR2. Inhibition of the lysosome resulted in increased intracellular accumulation of AVPR2-L170P, indicating that AVPR2-L170P is downregulated via the lysosome. Inhibition of the proteasome resulted in plasma membrane localization of AVPR2-L170P, although the overall levels of AVPR2-L170P were unchanged.
This item appears in the following Collection(s)
- Academic publications [238586]
- Faculty of Medical Sciences [90409]
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