ArticleProceedings of the National Academy of Sciences of the United States of America2008
Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 48 citations in OpenAlex.
- It Takes a Village: The Multifaceted Immune Response toFrontiers in immunology · 2022Review
- Immune Cell Degranulation in Fungal Host Defence.Journal of fungi (Basel, Switzerland) · 2021Review
- Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity.Nature biomedical engineering · 2019Article
- Review
- Human Granzyme B Based Targeted Cytolytic Fusion Proteins.Biomedicines · 2018Review
- Impairment of Fas-ligand-caveolin-1 interaction inhibits Fas-ligand translocation to rafts and Fas-ligand-induced cell death.Cell death & disease · 2018Article
- Efficacy of an adapted granzyme B-based anti-CD30 cytolytic fusion protein against PI-9-positive classical Hodgkin lymphoma cells in a murine model.Blood cancer journal · 2013Article
- EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells.PloS one · 2013Article
- Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice.Journal of virology · 2012Article
- Granzyme B-induced neurotoxicity is mediated via activation of PAR-1 receptor and Kv1.3 channel.PloS one · 2012Article
- Article
- Article
- Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How granzymes gain entry into the cytosol of target cells during killer cell attack has been the subject of several studies in the past, but the effective delivery mechanism during target cell encounter has not been clarified. Here we show that granzyme B (GzmB) mutants lacking binding to negatively charged, essentially heparan-sulfate-containing membrane receptors are poorly endocytosed yet are delivered to the cytosol with efficacy similar to that of WT GzmB. In a cell-based system GzmB-deficient natural killer cells provided perforin (pfn) by natural polarized secretion and synergized with externally added GzmB. Whereas receptor (heparan sulfate)-dependent endocytosis was dispensable, delivery of larger cargo like that of GzmB fusion proteins and GzmB-antibody complexes was restricted by their size. Our data support the model in which granzymes are primarily translocated through repairable membrane pores of finite size and not by the disruption of endocytosed vesicles. We conclude that structurally related translocators, i.e., perforin and cholesterol-dependent cytolysins, deliver deathly cargo across host cell membranes in a similar manner.
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Registered trials
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.