Evidence map›Paper›PMID 25146929›Full record

ArticleCell death and differentiation2015

Perforin oligomers form arcs in cellular membranes: a locus for intracellular delivery of granzymes.

S S Metkar, M Marchioretto, V Antonini, L Lunelli, B Wang, R J C Gilbert, G Anderluh, R Roth, M Pooga, J Pardo and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2015. 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
5.8field-weighted citation impact, top 3% 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

41 citing papers in PubMed, 73 citations in OpenAlex.

  1. AFM to Study Pore-Forming Proteins.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025
    Review
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  12. Mitochondrial outer membrane permeabilization at the single molecule level.Cellular and molecular life sciences : CMLS · 2021
    Review
  13. Article
  14. Review
  15. License to Kill: When iNKT Cells Are Granted the Use of Lethal Cytotoxicity.International journal of molecular sciences · 2020
    Review
  16. Article
  17. Review
  18. Article
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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

13 authors at 7 institutions in 6 countries.

S S MetkarNorthShore University Health Systems Research Institute and University of Chicago, Evanston, IL, USA.
M Marchioretto1] Consiglio Nazionale delle Ricerche, Istituto di Biofisica & Fondazione Bruno Kessler Via alla Cascata 56/C, Trento 38123, Italy [2] Center for Integrative Biology CIBIO, University of Trento Via delle Regole, 101 Mattarello (Trento) 38123, Italy.
V AntoniniConsiglio Nazionale delle Ricerche, Istituto di Biofisica & Fondazione Bruno Kessler Via alla Cascata 56/C, Trento 38123, Italy.
L LunelliConsiglio Nazionale delle Ricerche, Istituto di Biofisica & Fondazione Bruno Kessler Via alla Cascata 56/C, Trento 38123, Italy.
B WangNorthShore University Health Systems Research Institute and University of Chicago, Evanston, IL, USA.
R J C GilbertDivision of Structural Biology, Henry Wellcome Building for Genomic Medicine, Oxford, UK.
G AnderluhLaboratory of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, Ljublana, Slovenia.
R RothDepartment of Cell Biology and Physiology, Washington University in Saint Louis, 660 S. Euclid Avenue, St Louis, MO, USA.
M PoogaInstitute of Molecular and Cell Biology, University of Tartu, Riia Str 23, Tartu, Estonia.
J PardoDepartment of Biochemistry and Molecular and Cell Biology, Biomedical Research Centre of Aragon (CIBA), IIS Aragon and Nanoscience Institute of Aragon (INA), University of Zaragoza/ARAID Foundation, 50009 Zaragoza, Spain.
J E HeuserDepartment of Cell Biology and Physiology, Washington University in Saint Louis, 660 S. Euclid Avenue, St Louis, MO, USA.
M D SerraConsiglio Nazionale delle Ricerche, Istituto di Biofisica & Fondazione Bruno Kessler Via alla Cascata 56/C, Trento 38123, Italy.
C J FroelichNorthShore University Health Systems Research Institute and University of Chicago, Evanston, IL, USA.
NorthShore University HealthSystem · USWashington University in St. Louis · USCentre for Human Genetics · GBFundacion Agencia Aragonesa para la Investigacion y el Desarrollo · ESNational Institute of Chemistry · SIUniversity of Tartu · EEUniversity of Trento · IT

Funding

Molecular Mechanism of Granule-mediated ApoptosisR01AI044941 · NIAID · NORTHSHORE UNIV HEALTHSYSTEM RES INST · PI FROELICH, CHRISTOPHER JOHN · 2000 to 2010
$3.0M
NIAID NIH HHS R01 AI044941
6 · The paper itself

Abstract

Perforin-mediated cytotoxicity is an essential host defense, in which defects contribute to tumor development and pathogenic disorders including autoimmunity and autoinflammation. How perforin (PFN) facilitates intracellular delivery of pro-apoptotic and inflammatory granzymes across the bilayer of targets remains unresolved. Here we show that cellular susceptibility to granzyme B (GzmB) correlates with rapid PFN-induced phosphatidylserine externalization, suggesting that pores are formed at a protein-lipid interface by incomplete membrane oligomers (or arcs). Supporting a role for these oligomers in protease delivery, an anti-PFN antibody (pf-80) suppresses necrosis but increases phosphatidylserine flip-flop and GzmB-induced apoptosis. As shown by atomic force microscopy on planar bilayers and deep-etch electron microscopy on mammalian cells, pf-80 increases the proportion of arcs which correlates with the presence of smaller electrical conductances, while large cylindrical pores decline. PFN appears to form arc structures on target membranes that serve as minimally disrupting conduits for GzmB translocation. The role of these arcs in PFN-mediated pathology warrants evaluation where they may serve as novel therapeutic targets.

Indexed as

ApoptosisCell Membrane PermeabilityAntibodies, NeutralizingCell MembraneGranzymesHumansJurkat CellsMultiprotein ComplexesNecrosisPerforinProtein TransportAntibodies, NeutralizingGranzymesGZMB protein, humanMultiprotein ComplexesPerforinPRF1 protein, human

Identifiers

PMID25146929
PMCPMC4262768
OpenAlexW1978963713

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.