Evidence map›Paper›PMID 25770213›Full record

ArticleThe Journal of biological chemistry2015

Sodium-calcium exchanger 1 regulates epithelial cell migration via calcium-dependent extracellular signal-regulated kinase signaling.

Sona Lakshme Balasubramaniam, Anilkumar Gopalakrishnapillai, Vimal Gangadharan, Randall L Duncan, Sonali P Barwe

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. The context-dependent role of the NaPflugers Archiv : European journal of physiology · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Role of endogenous ouabain in the etiology of bipolar disorder.International journal of bipolar disorders · 2021
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia.Cold Spring Harbor molecular case studies · 2016
    Article
  13. Article
  14. Article
  15. Ion dependence of Na-K-ATPase-mediated epithelial cell adhesion and migration.American journal of physiology. Cell physiology · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Sona Lakshme BalasubramaniamFrom the Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803 and Department of Biological Sciences, University of Delaware, Newark, Delaware 19716.
Anilkumar GopalakrishnapillaiFrom the Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803 and.
Vimal GangadharanDepartment of Biological Sciences, University of Delaware, Newark, Delaware 19716.
Randall L DuncanDepartment of Biological Sciences, University of Delaware, Newark, Delaware 19716.
Sonali P BarweFrom the Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803 and Department of Biological Sciences, University of Delaware, Newark, Delaware 19716 barwe@medsci.udel.edu.
University of Delaware · USAlfred I. duPont Hospital for Children · US

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI Anjana Narayan Bhat · 2012 to 2026
$67.2M
Subproject Title: Clinical Research Education, Mentoring and Career Development CoreU54GM104941 · NIGMS · UNIVERSITY OF DELAWARE · PI Megan M Wenner · 2013 to 2026
$60.5M
Center for Pediatric ResearchP20GM103464 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2012 to 2014
$5.6M
NIGMS NIH HHS 8 P20GM103446-13NIGMS NIH HHS P20 GM103446NIGMS NIH HHS P20 GM103464NIGMS NIH HHS P20GM103464NIGMS NIH HHS U54 GM104941NIGMS NIH HHS U54GM104941
6 · The paper itself

Abstract

Na(+)/Ca(2+) exchanger-1 (NCX1) is a major calcium extrusion mechanism in renal epithelial cells enabling the efflux of one Ca(2+) ion and the influx of three Na(+) ions. The gradient for this exchange activity is provided by Na,K-ATPase, a hetero-oligomer consisting of a catalytic α-subunit and a regulatory β-subunit (Na,K-β) that also functions as a motility and tumor suppressor. We showed earlier that mice with heart-specific ablation (KO) of Na,K-β had a specific reduction in NCX1 protein and were ouabain-insensitive. Here, we demonstrate that Na,K-β associates with NCX1 and regulates its localization to the cell surface. Madin-Darby canine kidney cells with Na,K-β knockdown have reduced NCX1 protein and function accompanied by 2.1-fold increase in free intracellular calcium and a corresponding increase in the rate of cell migration. Increased intracellular calcium up-regulated ERK1/2 via calmodulin-dependent activation of PI3K. Both myosin light chain kinase and Rho-associated kinase acted as mediators of ERK1/2-dependent migration. Restoring NCX1 expression in β-KD cells reduced migration rate and ERK1/2 activation, suggesting that NCX1 functions downstream of Na,K-β in regulating cell migration. In parallel, inhibition of NCX1 by KB-R7943 in Madin-Darby canine kidney cells, LLC-PK1, and human primary renal epithelial cells (HREpiC) increased ERK1/2 activation and cell migration. This increased migration was associated with high myosin light chain phosphorylation by PI3K/ERK-dependent mechanism in HREpiC cells. These data confirm the role of NCX1 activity in regulating renal epithelial cell migration.

Indexed as

AnimalsAnti-Arrhythmia AgentsCalciumCell MovementDogsEnzyme ActivationHumansKidneyMadin Darby Canine Kidney CellsMAP Kinase Signaling SystemMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Myosin-Light-Chain KinasePhosphorylationrho-Associated Kinases2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonateAnti-Arrhythmia AgentsCalciumMAPK1 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Myosin-Light-Chain Kinaserho-Associated KinasesSodium-Calcium Exchangersodium-calcium exchanger 1Sodium-Potassium-Exchanging ATPaseThioureaCalciumCell MigrationExtracellular Signal-regulated Kinase (ERK)Na+/K+-ATPaseNCX1Sodium-Calcium Exchange

Identifiers

PMID25770213
PMCPMC4432267
OpenAlexW2006495215

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.