Evidence map›Paper›PMID 20663869›Full record

ArticleThe Journal of biological chemistry2010

Cys palmitoylation of the beta subunit modulates gating of the epithelial sodium channel.

Gunhild M Mueller, Ahmad B Maarouf, Carol L Kinlough, Nan Sheng, Ossama B Kashlan, Sora Okumura, Sarah Luthy, Thomas R Kleyman, Rebecca P Hughey

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
–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

41 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Epithelial NaComprehensive Physiology · 2024
    Review
  5. Article
  6. Article
  7. The Epithelial Sodium Channel-An Underestimated Drug Target.International journal of molecular sciences · 2023
    Review
  8. Review
  9. Palmitoylation of Voltage-Gated Ion Channels.International journal of molecular sciences · 2022
    Review
  10. Review
  11. Review
  12. The Journal of biological chemistry · 2020
    Article
  13. Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020
    Review
  14. Murine epithelial sodium (NaThe Journal of biological chemistry · 2019
    Article
  15. Review
  16. Article
  17. Epithelial NaAnnual review of physiology · 2018
    Review
  18. Article
  19. Article
  20. 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

9 authors.

Gunhild M MuellerRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Ahmad B Maarouf
Carol L Kinlough
Nan Sheng
Ossama B Kashlan
Sora Okumura
Sarah Luthy
Thomas R Kleyman
Rebecca P Hughey

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Sodium Channel BiogenesisR01DK065161 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUGHEY, REBECCA P, KLEYMAN, THOMAS R · 2004 to 2013
$2.8M
Organization and Structure of ENaC Transmembrane SegmentsK01DK078734 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KASHLAN, OSSAMA B · 2008 to 2012
$706k
Sodium Channel BiogenesisR56DK065161 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUGHEY, REBECCA P, KLEYMAN, THOMAS R · 2008 to 2008
$226k
NIDDK NIH HHS DK079307NIDDK NIH HHS DK65161NIDDK NIH HHS K01 DK078734NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK065161NIDDK NIH HHS R56 DK065161
6 · The paper itself

Abstract

The epithelial Na(+) channel (ENaC) is comprised of three homologous subunits (α, β, and γ) that have a similar topology with two transmembrane domains, a large extracellular region, and cytoplasmic N and C termini. Although ENaC activity is regulated by a number of factors, palmitoylation of its cytoplasmic Cys residues has not been previously described. Fatty acid-exchange chemistry was used to determine whether channel subunits were Cys-palmitoylated. We observed that only the β and γ subunits were modified by Cys palmitoylation. Analyses of ENaCs with mutant β subunits revealed that Cys-43 and Cys-557 were palmitoylated. Xenopus oocytes expressing ENaC with a β C43A,C557A mutant had significantly reduced amiloride-sensitive whole cell currents, enhanced Na(+) self-inhibition, and reduced single channel P(o) when compared with wild-type ENaC, while membrane trafficking and levels of surface expression were unchanged. Computer modeling of cytoplasmic domains indicated that β Cys-43 is in proximity to the first transmembrane α helix, whereas β Cys-557 is within an amphipathic α-helix contiguous with the second transmembrane domain. We propose that β subunit palmitoylation modulates channel gating by facilitating interactions between cytoplasmic domains and the plasma membrane.

Indexed as

AmilorideAmino Acid SubstitutionAnimalsCell LineCell MembraneComputer SimulationDogsEpithelial Sodium ChannelsIon Channel GatingLipoylationMiceModels, MolecularMutationMutation, MissenseOocytesProtein Structure, SecondaryAmilorideEpithelial Sodium ChannelsSodiumSodium Channel Blockers

Identifiers

PMID20663869
PMCPMC2945538

What OpenQuestion holds

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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.