Evidence map›Paper›PMID 21388961›Full record

ArticleThe Journal of biological chemistry2011

Insights into the mechanism of pore opening of acid-sensing ion channel 1a.

Lindsey A Tolino, Sora Okumura, Ossama B Kashlan, Marcelo D Carattino

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Review
  2. Epithelial NaComprehensive Physiology · 2024
    Review
  3. Article
  4. Article
  5. ASIC3 fine-tunes bladder sensory signaling.American journal of physiology. Renal physiology · 2018
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. ASICs and neuropeptides.Neuropharmacology · 2015
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. ENaC regulation by proteases and shear stress.Current molecular pharmacology · 2013
    Review
  19. Gating transitions in the palm domain of ASIC1a.The Journal of biological chemistry · 2013
    Article
  20. Review
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

4 authors.

Lindsey A TolinoRenal-Electrolyte Division, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Sora Okumura
Ossama B Kashlan
Marcelo D Carattino

Funding

Conformational rearrangements underlying ASIC1a gatingR01DK084060 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARATTINO, MARCELO DANIEL · 2010 to 2014
$1.6M
Organization and Structure of ENaC Transmembrane SegmentsK01DK078734 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KASHLAN, OSSAMA B · 2008 to 2012
$706k
NIDDK NIH HHS DK078734NIDDK NIH HHS K01 DK078734NIDDK NIH HHS R01 DK084060
6 · The paper itself

Abstract

Acid-sensing ion channels (ASICs) are trimeric cation channels that undergo activation and desensitization in response to extracellular acidification. The underlying mechanism coupling proton binding in the extracellular region to pore gating is unknown. Here we probed the reactivity toward methanethiosulfonate (MTS) reagents of channels with cysteine-substituted residues in the outer vestibule of the pore of ASIC1a. We found that positively-charged MTS reagents trigger pore opening of G428C. Scanning mutagenesis of residues in the region preceding the second transmembrane spanning domain indicated that the MTSET-modified side chain of Cys at position 428 interacts with Tyr-424. This interaction was confirmed by double-mutant cycle analysis. Strikingly, Y424C-G428C monomers were associated by intersubunit disulfide bonds and were insensitive to MTSET. Despite the spatial constraints introduced by these intersubunit disulfide bonds in the outer vestibule of the pore, Y424C-G428C transitions between the resting, open, and desensitized states in response to extracellular acidification. This finding suggests that the opening of the ion conductive pathway involves coordinated rotation of the second transmembrane-spanning domains.

Indexed as

Acid Sensing Ion ChannelsAmino Acid SubstitutionAnimalsDisulfidesIndicators and ReagentsIon TransportMesylatesMiceMutagenesisMutation, MissenseNerve Tissue ProteinsProtein Structure, TertiarySodium ChannelsXenopus laevisAcid Sensing Ion ChannelsASIC1 protein, mouseDisulfidesIndicators and ReagentsMesylatesmethanethiosulfonateNerve Tissue ProteinsSodium Channels

Identifiers

PMID21388961
PMCPMC3091236

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.