Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

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dc.contributor.authorBaltzer, Sandrine
dc.contributor.authorBulatov, Timur
dc.contributor.authorSchmied, Christopher
dc.contributor.authorKrämer, Andreas
dc.contributor.authorBerger, Benedict-Tilman
dc.contributor.authorOder, Andreas
dc.contributor.authorWalker-Gray, Ryan
dc.contributor.authorKuschke, Christin
dc.contributor.authorZühlke, Kerstin
dc.contributor.authorEichhorst, Jenny
dc.contributor.authorLehmann, Martin
dc.contributor.authorKnapp, Stefan
dc.contributor.authorWeston, John
dc.contributor.authorvon Kries, Jens Peter
dc.contributor.authorSüssmuth, Roderich D.
dc.contributor.authorKlussmann, Enno
dc.date.accessioned2022-10-18T07:46:59Z
dc.date.available2022-10-18T07:46:59Z
dc.date.issued2022-01-11
dc.date.updated2022-09-04T00:42:58Z
dc.description.abstractThe cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.
dc.description.sponsorshipBMBF, 16GW0179K, Verbundprojekt: Validierung der Interaktion zwischen AKAP18 und PKA bei Herzinsuffizienz -AKAP18-PKA-; Teilvorhaben: Validierung der Interaktion als pharmakologische Zielstruktur
dc.description.sponsorshipDFG, 394046635, SFB 1365: Nephroprotektion
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/17589
dc.identifier.urihttps://doi.org/10.14279/depositonce-16370
dc.language.isoen
dc.rightsLicensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc570 Biowissenschaften; Biologiede
dc.subject.otherAURKA
dc.subject.otherAQP2
dc.subject.otherAVP
dc.subject.othercofilin-1
dc.subject.otheractin cytoskeleton
dc.titleAurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells
dc.typeArticle
dc.type.versionpublishedVersion
dcterms.bibliographicCitation.articlenumber763
dcterms.bibliographicCitation.doi10.3390/ijms23020763
dcterms.bibliographicCitation.issue2
dcterms.bibliographicCitation.journaltitleInternational Journal of Molecular Sciences
dcterms.bibliographicCitation.originalpublishernameMDPI
dcterms.bibliographicCitation.originalpublisherplaceBasel
dcterms.bibliographicCitation.volume23
tub.accessrights.dnbfree
tub.affiliationFak. 2 Mathematik und Naturwissenschaften::Inst. Chemie::FG Biologische Chemie
tub.publisher.universityorinstitutionTechnische Universität Berlin
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