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

Overview of attention for article published in PLOS ONE, January 2018
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  • Above-average Attention Score compared to outputs of the same age (54th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

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Title
An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells
Published in
PLOS ONE, January 2018
DOI 10.1371/journal.pone.0191423
Pubmed ID
Authors

Katharina Schrade, Jessica Tröger, Adeeb Eldahshan, Kerstin Zühlke, Kamal R. Abdul Azeez, Jonathan M. Elkins, Martin Neuenschwander, Andreas Oder, Mohamed Elkewedi, Sarah Jaksch, Karsten Andrae, Jinliang Li, Joao Fernandes, Paul Markus Müller, Stephan Grunwald, Stephen F. Marino, Tanja Vukićević, Jenny Eichhorst, Burkhard Wiesner, Marcus Weber, Michael Kapiloff, Oliver Rocks, Oliver Daumke, Thomas Wieland, Stefan Knapp, Jens Peter von Kries, Enno Klussmann

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.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 12%
Professor 3 12%
Researcher 3 12%
Student > Ph. D. Student 3 12%
Other 2 8%
Other 5 19%
Unknown 7 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 23%
Agricultural and Biological Sciences 5 19%
Pharmacology, Toxicology and Pharmaceutical Science 2 8%
Medicine and Dentistry 2 8%
Psychology 1 4%
Other 3 12%
Unknown 7 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 January 2019.
All research outputs
#7,544,865
of 23,018,998 outputs
Outputs from PLOS ONE
#90,308
of 196,226 outputs
Outputs of similar age
#155,319
of 440,577 outputs
Outputs of similar age from PLOS ONE
#1,500
of 3,479 outputs
Altmetric has tracked 23,018,998 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 196,226 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.2. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 440,577 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 3,479 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.