Evidence map›Paper›PMID 27402760›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption.

Jennifer L Whiting, Leah Ogier, Katherine A Forbush, Paula Bucko, Janani Gopalan, Ole-Morten Seternes, Lorene K Langeberg, John D Scott

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Aquaporins in Urinary System.Advances in experimental medicine and biology · 2023
    Article
  14. Expression Regulation and Trafficking of Aquaporins.Advances in experimental medicine and biology · 2023
    Review
  15. Tubular-specific CDK12 knockout causes a defect in urine concentration due to premature cleavage of the slc12a1 gene.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  16. LRBA is essential for urinary concentration and body water homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. A multiscale model of the regulation of aquaporin 2 recycling.NPJ systems biology and applications · 2022
    Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Jennifer L WhitingHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195.
Leah OgierHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195.
Katherine A ForbushHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195.
Paula BuckoHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195.
Janani GopalanDepartment of Pharmacology, University of Washington, Seattle, WA 98195.
Ole-Morten SeternesHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195.
Lorene K LangebergHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195.
John D ScottHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Pharmacology, University of Washington, Seattle, WA 98195 scottjdw@uw.edu.

Funding

Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETSP01DK054441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1999 to 2017
$27.3M
Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
Local Signaling in Diabetic ComorbiditiesR01DK105542 · NIDDK · UNIVERSITY OF WASHINGTON · PI SCOTT, JOHN D · 2015 to 2018
$1.4M
NIDDK NIH HHS P01 DK054441NIDDK NIH HHS R01 DK105542
6 · The paper itself

Abstract

Filtration through the kidney eliminates toxins, manages electrolyte balance, and controls water homeostasis. Reabsorption of water from the luminal fluid of the nephron occurs through aquaporin-2 (AQP2) water pores in principal cells that line the kidney-collecting duct. This vital process is impeded by formation of an "actin barrier" that obstructs the passive transit of AQP2 to the plasma membrane. Bidirectional control of AQP2 trafficking is managed by hormones and signaling enzymes. We have discovered that vasopressin-independent facets of this homeostatic mechanism are under the control of A-Kinase Anchoring Protein 220 (AKAP220; product of the Akap11 gene). CRISPR/Cas9 gene editing and imaging approaches show that loss of AKAP220 disrupts apical actin networks in organoid cultures. Similar defects are evident in tissue sections from AKAP220-KO mice. Biochemical analysis of AKAP220-null kidney extracts detected reduced levels of active RhoA GTPase, a well-known modulator of the actin cytoskeleton. Fluorescent imaging of kidney sections from these genetically modified mice revealed that RhoA and AQP2 accumulate at the apical surface of the collecting duct. Consequently, these animals are unable to appropriately dilute urine in response to overhydration. We propose that membrane-proximal signaling complexes constrained by AKAP220 impact the actin barrier dynamics and AQP2 trafficking to ensure water homeostasis.

Indexed as

Renal ReabsorptionActinsA Kinase Anchor ProteinsAnimalsAquaporin 2FemaleHomeostasisKidneyKidney Tubules, CollectingMaleMice, KnockoutOrgan Culture TechniquesrhoA GTP-Binding ProteinWaterActinsAkap11 protein, mouseA Kinase Anchor ProteinsAquaporin 2rhoA GTP-Binding ProteinWaterA-Kinase Anchoring Proteinkidney physiologysignal transduction

Identifiers

PMID27402760
PMCPMC4968721

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.