ArticleProceedings of the National Academy of Sciences of the United States of America2010
Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Identification of Potential Therapeutic Targets Against Anthrax-Toxin-Induced Liver and Heart Damage.Toxins · 2025Article
- Targeting canine mammary neoplastic epithelial cells with a reengineered anthrax toxin: first study.Veterinary research communications · 2024Article
- Early Circulating Edema Factor in Inhalational Anthrax Infection: Does It Matter?Microorganisms · 2024Article
- Anthrax Toxin Detection: From in Vivo Studies to Diagnostic Applications.Microorganisms · 2020Review
- Article
- Anthrax toxin receptor 1/tumor endothelial marker 8 promotes gastric cancer progression through activation of the PI3K/AKT/mTOR signaling pathway.Cancer science · 2020Article
- The role of anthrax toxin protein receptor 1 as a new mechanosensor molecule and its mechanotransduction in BMSCs under hydrostatic pressure.Scientific reports · 2019Article
- The Anthrax Toxin Receptor 1 (ANTXR1) Is Enriched in Pancreatic Cancer Stem Cells Derived from Primary Tumor Cultures.Stem cells international · 2019Article
- The Ins and Outs of Anthrax Toxin.Toxins · 2016Review
- Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.Scientific reports · 2015Article
- Review
- A microfluidic live cell assay to study anthrax toxin induced cell lethality assisted by conditioned medium.Scientific reports · 2015Article
- Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.Matrix biology : journal of the International Society for Matrix Biology · 2015Article
- New insights into gastrointestinal anthrax infection.Trends in molecular medicine · 2015Review
- Anthrax prophylaxis: recent advances and future directions.Frontiers in microbiology · 2015Review
- An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis.Expert opinion on investigational drugs · 2015Review
- Anthrax lethal and edema toxins in anthrax pathogenesis.Trends in microbiology · 2014Review
- Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.PLoS pathogens · 2014Article
- Designing inhibitors of anthrax toxin.Expert opinion on drug discovery · 2014Review
- (19)F nuclear magnetic resonance and crystallographic studies of 5-fluorotryptophan-labeled anthrax protective antigen and effects of the receptor on stability.Biochemistry · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To kill macrophages, the lethal factor component of Bacillus anthracis toxin binds to a carrier protein (PA), which then interacts with the CMG2 receptor protein on the cell surface and is endocytosed into the cytoplasm. CMG2, as well as TEM8, a second PA receptor not present on macrophages, contain a von Willebrand A domain that is crucial for toxin binding. Here we report that integrin beta1, another cell surface von Willebrand A domain protein, can mediate and potentiate anthrax toxin endocytosis. By using microarray-based analysis to globally correlate gene expression profiles with toxin sensitivity, we associated toxin effects with the integrin-activating proteins osteopontin and CD44. Further study showed that PA binds to alpha4beta1- and alpha5beta1-integrin complexes, leading to their conjoint endocytosis, and also interacts-weakly relative to CMG2 but comparably to TEM8--with purified alpha5beta1 complex in vitro. Monoclonal antibody directed against beta1-integrin or its alpha integrin partners reduced PA/integrin endocytosis and anthrax toxin lethality, and hyaluronic acid--which interferes with CD44-mediated integrin activation--had similar effects. Remarkably, whereas deficiency of CMG2 protected macrophages from rapid killing by large toxin doses (>50 ng/mL), by 24 h the toxin-treated cells were dead. Such late killing of CMG2-deficient cells by high dose toxin as well as the late death observed during exposure of CMG2-producing macrophages to low-dose toxin (<1 ng/mL), was dependent on integrin function. Effects of inactivating both CMG2 and integrin were synergistic. Collectively, our findings argue strongly that beta1-integrin can both potentiate CMG2-mediated endocytosis and serve independently as a low-affinity PA receptor.
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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.