ArticleThe EMBO journal1999
An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46 citing papers in PubMed, 1 synthesis or guideline pooled it, 208 citations in OpenAlex.
- Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.The pharmacogenomics journal · 2020Pooled it
- Cysteine-mediated structural stabilization of the tetrameric GlpF.European biophysics journal : EBJ · 2026Article
- Quaternary arrangements of membrane proteins: an aquaporin case.Biochemical Society transactions · 2024Review
- Structural and functional analysis of aquaporin-2 mutants involved in nephrogenic diabetes insipidus.Scientific reports · 2023Article
- Anomalous Oligomerization Behavior ofInternational journal of molecular sciences · 2023Article
- Aquaporin splice variation differentially modulates channel function during marine teleost egg hydration.PloS one · 2023Article
- Mechanistic insights into the primary and secondary alterations of renal ion and water transport in the distal nephron.Journal of internal medicine · 2023Review
- Further evidence for functional recovery of AQP2 mutations associated with nephrogenic diabetes insipidus.Physiological reports · 2021Article
- A Vasopressin-Induced Change in Prostaglandin Receptor Subtype Expression Explains the Differential Effect of PGEFrontiers in physiology · 2021Article
- Review
- Identification ofJournal of the American Society of Nephrology : JASN · 2019Article
- Involvement of PDZ-SAP97 interactions in regulating AQP2 translocation in response to vasopressin in LLC-PKAmerican journal of physiology. Renal physiology · 2019Article
- Article
- Structural Basis for Mutations of Human Aquaporins Associated to Genetic Diseases.International journal of molecular sciences · 2018Article
- Hereditary Nephrogenic Diabetes Insipidus: Pathophysiology and Possible Treatment. An Update.International journal of molecular sciences · 2017Review
- Pharmacoperone rescue of vasopressin 2 receptor mutants reveals unexpected constitutive activity and coupling bias.PloS one · 2017Article
- Functional Recovery of AQP2 Recessive Mutations Through Hetero-Oligomerization with Wild-Type Counterpart.Scientific reports · 2016Article
- Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.Journal of the American Society of Nephrology : JASN · 2016Article
- Structural Determinants of Oligomerization of the Aquaporin-4 Channel.The Journal of biological chemistry · 2016Article
- The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells-a Potential Target for Pharmacological Intervention in Cardiovascular Diseases.Frontiers in pharmacology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, are caused by mutations in the aquaporin-2 (AQP2) gene. Missense AQP2 proteins in recessive NDI have been shown to be retarded in the endoplasmic reticulum, whereas AQP2-E258K, an AQP2 mutant in dominant NDI, was retained in the Golgi complex. In this study, we identified the molecular mechanisms underlying recessive and dominant NDI. Sucrose gradient centrifugation of rat and human kidney proteins and subsequent immunoblotting revealed that AQP2 forms homotetramers. When expressed in oocytes, wild-type AQP2 and AQP2-E258K also formed homotetramers, whereas AQP2-R187C, a mutant in recessive NDI, was expressed as a monomer. Upon co-injection, AQP2-E258K, but not AQP2-R187C, was able to heterotetramerize with wild-type AQP2. Since an AQP monomer is the functional unit and AQP2-E258K is a functional but misrouted water channel, heterotetramerization of AQP2-E258K with wild-type AQP2 and inhibition of further routing of this complex to the plasma membrane is the cause of dominant NDI. This case of NDI is the first example of a dominant disease in which the 'loss-of-function' phenotype is caused by an impaired routing rather than impaired function of the wild-type protein.
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