ArticlePloS one2018
An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- GLUT9b- and ABCG2-mediated collecting duct urate transport uncovers a vasopressin-independent mechanism of renal water reabsorption.The Journal of clinical investigation · 2026Article
- Review
- Investigating the Anticancer Activity of G-Rh1 Using In Silico and In Vitro Studies (A549 Lung Cancer Cells).Molecules (Basel, Switzerland) · 2022Article
- A multiscale model of the regulation of aquaporin 2 recycling.NPJ systems biology and applications · 2022Article
- Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.International journal of molecular sciences · 2022Article
- Disruptors of AKAP-Dependent Protein-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.Nature reviews. Nephrology · 2021Review
- AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems.Journal of the American Heart Association · 2020Review
- Review
- Review
- The role of A-kinase anchoring proteins in cardiac oxidative stress.Biochemical Society transactions · 2019Review
- Small molecules for modulating the localisation of the water channel aquaporin-2-disease relevance and perspectives for targeting local cAMP signalling.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking.Journal of the American Society of Nephrology : JASN · 2019Article
- An Antifungal for Antidiuresis?Journal of the American Society of Nephrology : JASN · 2019Article
- Vasopressin-aquaporin-2 pathway: recent advances in understanding water balance disorders.F1000Research · 2019Review
- In vitro expression and functional characterization of NPA motifs in aquaporins of Nosema bombycis.Parasitology research · 2018Article
- Form follows function: polymorphisms in mAKAP alter cardiac cAMP/PKA signaling.American journal of physiology. Heart and circulatory physiology · 2018Article
- Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System.Journal of cardiovascular development and disease · 2018Review
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.