Evidence map›Paper›PMID 23613968›Full record

ArticlePloS one2013

The second transmembrane domain of P2X7 contributes to dilated pore formation.

Chengqun Sun, Michelle E Heid, Peter A Keyel, Russell D Salter

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. P2XFrontiers in cellular neuroscience · 2021
    Review
  7. Review
  8. P2X7 Receptor Upregulation in Huntington's Disease Brains.Frontiers in molecular neuroscience · 2020
    Article
  9. Article
  10. Review
  11. Localization of the gate and selectivity filter of the full-length P2X7 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  12. Article
  13. Article
  14. Article
  15. Structural and molecular modeling features of P2X receptors.International journal of molecular sciences · 2014
    Review
  16. Article
  17. Two open states of P2X receptor channels.Frontiers in cellular neuroscience · 2013
    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 at 1 institution in 1 country.

Chengqun SunDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Michelle E Heid
Peter A Keyel
Russell D Salter
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
MECHANISMS OF DENDRITIC CELL BASED TUMOR IMMUNIZATIONP01CA073743 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FINN, OLIVERA J · 1998 to 2009
$12.3M
Training in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2M
Autoimmunity and Immunopathology Training ProgramT32AI089443 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHLOMCHIK, MARK J · 2010 to 2024
$6.6M
Immunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3M
Interaction of microvesicles and bacterial toxins with immune cellsR01AI072083 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SALTER, RUSSELL D. · 2007 to 2011
$1.8M
NCI NIH HHS CA073743NCI NIH HHS P01 CA073743NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904NCI NIH HHS T32 CA082084NCI NIH HHS T32CA82084NIAID NIH HHS 32AI089443NIAID NIH HHS AI072083NIAID NIH HHS R01 AI072083NIAID NIH HHS T32 AI060525NIAID NIH HHS T32AI060525NIAID NIH HHS T32 AI089443
6 · The paper itself

Abstract

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors.

Indexed as

Ion Channel GatingAdenosine TriphosphateAmino Acid SubstitutionAnimalsCell DeathCell MembraneCell Membrane PermeabilityCell SurvivalHEK293 CellsHumansIndolesMiceMice, Inbred C57BLPoint MutationProtein Structure, TertiaryRatsAdenosine TriphosphateDAPIIndolesReceptors, Purinergic P2X1Receptors, Purinergic P2X4Receptors, Purinergic P2X7

Identifiers

PMID23613968
PMCPMC3629090
OpenAlexW2072686851

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.