Functional analysis of AQP2 mutants found in patients with diabetes insipidus

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dc.contributor.authorKaraduman, Tugce
dc.contributor.authorOzcan Turkmen, Merve
dc.contributor.authorOzer, Emel Saglar
dc.contributor.authorErgin, Bora
dc.contributor.authorSaglam, Berk
dc.contributor.authorErdem Tuncdemir, Beril
dc.contributor.authorMergen, Hatice
dc.date.accessioned2024-02-23T13:59:41Z
dc.date.available2024-02-23T13:59:41Z
dc.date.issued2021
dc.departmentNEÜen_US
dc.description.abstractAquaporin-2 (AQP2) is a homotetrameric water channel responsible for the reabsorption of water in the main collecting duct cells of kidneys. Mutations in AQP2 gene induce nephrogenic diabetes insipidus (NDI), a pathogenic condition involving the maintenance of body water homeostasis, leading to excess urine production. Several hypotheses in the literature were confirmed by clinical and experimental observations regarding the role of these mutations in the pathogenesis of NDI. In this study, three mutations (A45T, R85X, and A147T) identified in NDI patients were analyzed using stably transfected Madin-Darby canine kidney (MDCK) cells and Xenopus laevis (X. laevis) oocyte expression system compared to the wt-AQP2. According to our study, the A45T-AQP2 protein is characterized by reduced half-life and targeting defects, therefore this mutant protein can be retained in the endoplasmic reticulum (ER). The mutation also causes the formation of a nonfunctional water channel. The R85X-AQP2 protein was not detected in immunoblot analysis, but the results of water permeability test data prove that this mutant protein cannot form a functional water channel. Despite its features such as partial false targeting and reduced half-life, A147T-AQP2 protein forms a semi-functional water channel. In a conclusion, studies on the intracellular functions of mutant water channels are important because these studies elucidate the mechanisms leading to disease phenotype and support development of pharmacological strategies related to pathological mechanisms.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [115S499]; Hacettepe University Scientific Research Project [BAP FHD-2018-16485]; TUBITAK [2211-E]en_US
dc.description.sponsorshipThis work was supported by the grants from Scientific and Technological Research Council of Turkey (TUBITAK; 115S499) and Hacettepe University Scientific Research Project (BAP FHD-2018-16485). TK was supported by TUBITAK (2211-E).en_US
dc.identifier.doi10.1007/s11756-021-00807-9
dc.identifier.endpage2776en_US
dc.identifier.issn0006-3088
dc.identifier.issn1336-9563
dc.identifier.issue9en_US
dc.identifier.scopus2-s2.0-85109312007en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage2767en_US
dc.identifier.urihttps://doi.org/10.1007/s11756-021-00807-9
dc.identifier.urihttps://hdl.handle.net/20.500.12452/11279
dc.identifier.volume76en_US
dc.identifier.wosWOS:000669159900001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofBiologiaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectDiabetes Insipidusen_US
dc.subjectAqp2en_US
dc.subjectMutationen_US
dc.subjectFunctional Analysisen_US
dc.titleFunctional analysis of AQP2 mutants found in patients with diabetes insipidusen_US
dc.typeArticleen_US

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