An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells

  1. Schrade, Katharina
  2. Tröger, Jessica
  3. Eldahshan, Adeeb
  4. Zühlke, Kerstin
  5. Abdul Azeez, Kamal R.
  6. Elkins, Jonathan M.
  7. Neuenschwander, Martin
  8. Oder, Andreas
  9. Elkewedi, Mohamed
  10. Jaksch, Sarah
  11. Andrae, Karsten
  12. Li, Jinliang
  13. Fernandes, Joao
  14. Müller, Paul Markus
  15. Grunwald, Stephan
  16. Marino, Stephen F.
  17. Vukićević, Tanja
  18. Eichhorst, Jenny
  19. Wiesner, Burkhard
  20. Weber, Marcus
  21. Kapiloff, Michael
  22. Rocks, Oliver
  23. Daumke, Oliver
  24. Wieland, Thomas
  25. Knapp, Stefan
  26. von Kries, Jens Peter
  27. Klussmann, Enno ORCID logo

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WeightNameValue
1000 Titel
  • An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells
1000 Autor/in
  1. Schrade, Katharina |
  2. Tröger, Jessica |
  3. Eldahshan, Adeeb |
  4. Zühlke, Kerstin |
  5. Abdul Azeez, Kamal R. |
  6. Elkins, Jonathan M. |
  7. Neuenschwander, Martin |
  8. Oder, Andreas |
  9. Elkewedi, Mohamed |
  10. Jaksch, Sarah |
  11. Andrae, Karsten |
  12. Li, Jinliang |
  13. Fernandes, Joao |
  14. Müller, Paul Markus |
  15. Grunwald, Stephan |
  16. Marino, Stephen F. |
  17. Vukićević, Tanja |
  18. Eichhorst, Jenny |
  19. Wiesner, Burkhard |
  20. Weber, Marcus |
  21. Kapiloff, Michael |
  22. Rocks, Oliver |
  23. Daumke, Oliver |
  24. Wieland, Thomas |
  25. Knapp, Stefan |
  26. von Kries, Jens Peter |
  27. Klussmann, Enno |
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2018-01-26
1000 Erschienen in
1000 Quellenangabe
  • 13(1):e0191423
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2018
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.pone.0191423 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786306/ |
1000 Ergänzendes Material
  • http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191423#sec025 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/U2NocmFkZSwgS2F0aGFyaW5h|https://frl.publisso.de/adhoc/creator/VHLDtmdlciwgSmVzc2ljYQ==|https://frl.publisso.de/adhoc/creator/RWxkYWhzaGFuLCBBZGVlYg==|https://frl.publisso.de/adhoc/creator/WsO8aGxrZSwgS2Vyc3Rpbg==|https://frl.publisso.de/adhoc/creator/QWJkdWwgQXplZXosIEthbWFsIFIu|https://frl.publisso.de/adhoc/creator/RWxraW5zLCBKb25hdGhhbiBNLg==|https://frl.publisso.de/adhoc/creator/TmV1ZW5zY2h3YW5kZXIsIE1hcnRpbg==|https://frl.publisso.de/adhoc/creator/T2RlciwgQW5kcmVhcw==|https://frl.publisso.de/adhoc/creator/RWxrZXdlZGksIE1vaGFtZWQ=|https://frl.publisso.de/adhoc/creator/SmFrc2NoLCBTYXJhaA==|https://frl.publisso.de/adhoc/creator/QW5kcmFlLCBLYXJzdGVu|https://frl.publisso.de/adhoc/creator/TGksIEppbmxpYW5n|https://frl.publisso.de/adhoc/creator/RmVybmFuZGVzLCBKb2Fv|https://frl.publisso.de/adhoc/creator/TcO8bGxlciwgUGF1bCBNYXJrdXM=|https://frl.publisso.de/adhoc/creator/R3J1bndhbGQsIFN0ZXBoYW4=|https://frl.publisso.de/adhoc/creator/TWFyaW5vLCBTdGVwaGVuIEYu|https://frl.publisso.de/adhoc/creator/VnVracSHZXZpxIcsIFRhbmph|https://frl.publisso.de/adhoc/creator/RWljaGhvcnN0LCBKZW5ueQ==|https://frl.publisso.de/adhoc/creator/V2llc25lciwgQnVya2hhcmQ=|https://frl.publisso.de/adhoc/creator/V2ViZXIsIE1hcmN1cw==|https://frl.publisso.de/adhoc/creator/S2FwaWxvZmYsIE1pY2hhZWw=|https://frl.publisso.de/adhoc/creator/Um9ja3MsIE9saXZlcg==|https://frl.publisso.de/adhoc/creator/RGF1bWtlLCBPbGl2ZXI=|https://frl.publisso.de/adhoc/creator/V2llbGFuZCwgVGhvbWFz|https://frl.publisso.de/adhoc/creator/S25hcHAsIFN0ZWZhbg==|https://frl.publisso.de/adhoc/creator/dm9uIEtyaWVzLCBKZW5zIFBldGVy|http://orcid.org/0000-0003-4004-5003
1000 Label
1000 Förderer
  1. Else Kröner-Fresenius-Stiftung |
  2. German-Israeli Foundation |
  3. German Centre for Cardio-vascular Research |
  4. Deutsche Forschungsgemeinschaft (DFG) |
  5. Bundesministerium für Bildung und Forschung (BMBF) |
1000 Fördernummer
  1. 2013_A145
  2. G.I.F. I-1210-286.13/2012
  3. DZHK 81X210012; B18-005 SE
  4. KL1415/7-1
  5. 16GW0179K
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. -
  5. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Else Kröner-Fresenius-Stiftung |
    1000 Förderprogramm -
    1000 Fördernummer 2013_A145
  2. 1000 joinedFunding-child
    1000 Förderer German-Israeli Foundation |
    1000 Förderprogramm -
    1000 Fördernummer G.I.F. I-1210-286.13/2012
  3. 1000 joinedFunding-child
    1000 Förderer German Centre for Cardio-vascular Research |
    1000 Förderprogramm -
    1000 Fördernummer DZHK 81X210012; B18-005 SE
  4. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer KL1415/7-1
  5. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung (BMBF) |
    1000 Förderprogramm -
    1000 Fördernummer 16GW0179K
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6406546.rdf
1000 Erstellt am 2018-01-30T11:18:15.317+0100
1000 Erstellt von 241
1000 beschreibt frl:6406546
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Aug 05 14:55:36 CEST 2021
1000 Objekt bearb. Thu Aug 05 14:55:35 CEST 2021
1000 Vgl. frl:6406546
1000 Oai Id
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