Evidence map›Paper›PMID 20038786›Full record

ArticleBlood2010

Perforin activates clathrin- and dynamin-dependent endocytosis, which is required for plasma membrane repair and delivery of granzyme B for granzyme-mediated apoptosis.

Jerome Thiery, Dennis Keefe, Saviz Saffarian, Denis Martinvalet, Michael Walch, Emmanuel Boucrot, Tomas Kirchhausen, Judy Lieberman

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

74 citing papers in PubMed, 127 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Natural infection of hybrid sturgeon (Frontiers in immunology · 2024
    Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Early Endosomes Act as Local Exocytosis Hubs to Repair Endothelial Membrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  18. Review
  19. Review
  20. Article

14 more citing papers are in PubMed but not listed here.

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.

Jerome ThieryProgram in Cellular and Molecular Medicine, Children's Hospital and Immune Disease Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Dennis Keefe
Saviz Saffarian
Denis Martinvalet
Michael Walch
Emmanuel Boucrot
Tomas Kirchhausen
Judy Lieberman
Boston Children's Hospital · USHarvard University · US

Funding

Mechanism of perforin activityR01AI063430 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI LIEBERMAN, JUDY · 2006 to 2010
$3.1M
NIAID NIH HHS AI063430NIAID NIH HHS R01 AI063430
6 · The paper itself

Abstract

Cytotoxic T lymphocytes and natural killer cells destroy target cells via the polarized exocytosis of lytic effector proteins, perforin and granzymes, into the immunologic synapse. How these molecules enter target cells is not fully understood. It is debated whether granzymes enter via perforin pores formed at the plasma membrane or whether perforin and granzymes are first endocytosed and granzymes are then released from endosomes into the cytoplasm. We previously showed that perforin disruption of the plasma membrane induces a transient Ca(2+) flux into the target cell that triggers a wounded membrane repair response in which lysosomes and endosomes donate their membranes to reseal the damaged membrane. Here we show that perforin activates clathrin- and dynamin-dependent endocytosis, which removes perforin and granzymes from the plasma membrane to early endosomes, preserving outer membrane integrity. Inhibiting clathrin- or dynamin-dependent endocytosis shifts death by perforin and granzyme B from apoptosis to necrosis. Thus by activating endocytosis to preserve membrane integrity, perforin facilitates granzyme uptake and avoids the proinflammatory necrotic death of a membrane-damaged cell.

Indexed as

AnimalsApoptosisCell MembraneClathrinDynaminsEndocytosisEndosomesGranzymesHeLa CellsHumansPerforinRatsClathrinDynaminsGranzymesGZMB protein, humanGzmb protein, ratPerforin

Identifiers

PMID20038786
PMCPMC2830763
OpenAlexW2164464853

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.