Evidence map›Paper›PMID 25767115›Full record

ArticleThe Journal of biological chemistry2015

Intracellular Na+ regulates epithelial Na+ channel maturation.

Elisa Heidrich, Marcelo D Carattino, Rebecca P Hughey, Joseph M Pilewski, Thomas R Kleyman, Mike M Myerburg

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 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Epithelial NaComprehensive Physiology · 2024
    Review
  2. Bile acids regulate the epithelial NaThe Journal of physiology · 2022
    Article
  3. Elevated intracellular NaProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  4. Paraoxonase 2 is an ER chaperone that regulates the epithelial NaAmerican journal of physiology. Cell physiology · 2022
    Article
  5. Cleavage state of γENaC in mouse and rat kidneys.American journal of physiology. Renal physiology · 2021
    Article
  6. Review
  7. Article
  8. Analyses of epithelial NaThe Journal of biological chemistry · 2019
    Article
  9. Article
  10. N-linked glycans are required on epithelial NaAmerican journal of physiology. Renal physiology · 2018
    Article
  11. Epithelial NaAnnual review of physiology · 2018
    Review
  12. Article
  13. Review
  14. 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

6 authors at 1 institution in 1 country.

Elisa HeidrichFrom the Division of Pulmonary, Allergy, and Critical Care Medicine.
Marcelo D CarattinoRenal-Electrolyte Division, and Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Rebecca P HugheyFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, Renal-Electrolyte Division, and.
Joseph M PilewskiFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Thomas R KleymanRenal-Electrolyte Division, and Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Mike M MyerburgFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, myerburgm@upmc.edu.
University of Pittsburgh · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Translational StudiesP30DK072506 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWIATECKA-URBAN, AGNIESZKA · 2005 to 2017
$12.5M
Biomechanical Regulation of Renal Ion TransportersR37DK051391 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2006 to 2015
$3.2M
Th2 inflammation promotes airway surface liquid dehydrationR01HL112863 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MYERBURG, MICHAEL M · 2012 to 2016
$1.9M
SODIUM CHANNELS IN THE MAMMALIAN URINARY BLADDERR01DK051391 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R. · 1996 to 2005
$1.5M
Altered Proteolytic Processing of ENaC in the Pathogenesis of Cystic FibrosisK08HL087932 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MYERBURG, MICHAEL M · 2008 to 2012
$625k
NHLBI NIH HHS K08 HL087932NHLBI NIH HHS R01 HL112863NIDDK NIH HHS P30 DK072506NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK051391NIDDK NIH HHS R37 DK051391
6 · The paper itself

Abstract

Epithelial Na(+) channel (ENaC) function is regulated by the intracellular Na(+) concentration ([Na(+)]i) through a process known as Na(+) feedback inhibition. Although this process is known to decrease the expression of proteolytically processed active channels on the cell surface, it is unknown how [Na(+)]i alters ENaC cleavage. We show here that [Na(+)]i regulates the posttranslational processing of ENaC subunits during channel biogenesis. At times when [Na(+)]i is low, ENaC subunits develop mature N-glycans and are processed by proteases. Conversely, glycan maturation and sensitivity to proteolysis are reduced when [Na(+)]i is relatively high. Surface channels with immature N-glycans were not processed by endogenous channel activating proteases, nor were they sensitive to cleavage by exogenous trypsin. Biotin chase experiments revealed that the immature surface channels were not converted into mature cleaved channels following a reduction in [Na(+)]i. The hypothesis that [Na(+)]i regulates ENaC maturation within the biosynthetic pathways is further supported by the finding that Brefeldin A prevented the accumulation of processed surface channels following a reduction in [Na(+)]i. Therefore, increased [Na(+)]i interferes with ENaC N-glycan maturation and prevents the channel from entering a state that allows proteolytic processing.

Indexed as

Epithelial Sodium ChannelsHumansIntracellular SpacePeptide HydrolasesPolysaccharidesProtein Processing, Post-TranslationalSodiumEpithelial Sodium ChannelsPeptide HydrolasesPolysaccharidesSodiumEpithelial Sodium Channel (ENaC)Posttranslational Modification (PTM)ProteaseProteoglycanSodium Transport

Identifiers

PMID25767115
PMCPMC4416860
OpenAlexW2124666663

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.