Evidence map›Paper›PMID 28726636›Full record

ArticleThe Journal of biological chemistry2017

Live-cell visualization of gasdermin D-driven pyroptotic cell death.

Joseph K Rathkey, Bryan L Benson, Steven M Chirieleison, Jie Yang, Tsan S Xiao, George R Dubyak, Alex Y Huang, Derek W Abbott

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Molecular probes for monitoring pyroptosis: design, imaging and theranostic application.Apoptosis : an international journal on programmed cell death · 2024
    Review
  11. Article
  12. The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  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

8 authors at 2 institutions in 1 country.

Joseph K RathkeyFrom the Department of Pathology.
Bryan L BensonFrom the Department of Pathology.
Steven M ChirieleisonFrom the Department of Pathology.
Jie YangFrom the Department of Pathology.
Tsan S XiaoFrom the Department of Pathology.
George R Dubyakthe Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Alex Y HuangFrom the Department of Pathology.
Derek W AbbottFrom the Department of Pathology, dwa4@case.edu.ORCID 0000-0003-4387-8094
Case Western Reserve University · USUniversity School · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Ubiquitination Pathways Mediating Chronic Intestinal InflammationP01DK091222 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI PIZARRO, THERESA TORRES · 2011 to 2020
$16.5M
Innate Immune Signal Transduction Specificity in Inflammatory DiseaseR01GM086550 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI ABBOTT, DEREK W · 2009 to 2020
$3.8M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
NRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9M
Clinical and Translational Science Collaborative of ClevelandTL1TR000441 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$2.8M
Case Western Reserve University/Cleveland Clinic CTSA (TL1)TL1RR024991 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$2.1M
Training in Neurodegenerative DiseasesT32NS077888 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI Xiongwei Zhu · 2013 to 2026
$1.8M
Acquisition of a Leica TCS SP5 Confocal Microscope For A Multi-User FacilityS10OD016164 · OD · CASE WESTERN RESERVE UNIVERSITY · PI CONRAD, PATRICIA A · 2013 to 2013
$597k
Using Microfluidics to Investigate Mechanisms of Leukocyte Intravascular CrawlingF31NS096857 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI BENSON, BRYAN LAUCK · 2017 to 2018
$69k
NCATS NIH HHS TL1 TR000441NCATS NIH HHS TL1 TR002549NCATS NIH HHS UL1 TR000439NCRR NIH HHS TL1 RR024991NIAID NIH HHS T32 AI089474NIDDK NIH HHS P01 DK091222NIGMS NIH HHS R01 GM086550NIGMS NIH HHS T32 GM007250NIH HHS S10 OD016164NINDS NIH HHS F31 NS096857NINDS NIH HHS T32 NS077888
6 · The paper itself

Abstract

Pyroptosis is a form of cell death important in defenses against pathogens that can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, GSDMD (gasdermin D), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD. In this work, we performed mutagenesis and molecular modeling to strategically place tags and fluorescent proteins within GSDMD that support native pyroptosis and facilitate live-cell imaging of pyroptotic cell death. Here, we demonstrate that these fusion proteins are cleaved by caspases-1 and -11 at Asp-276. Mutations that disrupted the predicted p30-p20 autoinhibitory interface resulted in GSDMD aggregation, supporting the oligomerizing activity of these mutations. Furthermore, we show that these novel GSDMD fusions execute inflammasome-dependent pyroptotic cell death in response to multiple stimuli and allow for visualization of the morphological changes associated with pyroptotic cell death in real time. This work therefore provides new tools that not only expand the molecular understanding of pyroptosis but also enable its direct visualization.

Indexed as

Models, BiologicalPyroptosisAmino Acid SubstitutionAnimalsCaspase 1CaspasesCaspases, InitiatorCell Line, TransformedGasderminsHEK293 CellsHumansInflammasomesIntracellular Signaling Peptides and ProteinsLuminescent ProteinsMacrophagesMiceCASP4 protein, humanCASP5 protein, humanCaspase 1CaspasesCaspases, InitiatorGasderminsGSDMD protein, humanInflammasomesIntracellular Signaling Peptides and ProteinsLuminescent ProteinsNeoplasm ProteinsPeptide FragmentsPhosphate-Binding ProteinsRecombinant Fusion Proteinscaspasecaspase 1 (CASP1)cell deathGasdermin Dinflammasomeinflammationinnate immunityporepyroptosis

Identifiers

PMID28726636
PMCPMC5582855
OpenAlexW2737470345

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.