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Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor.
Heather M Scobie1, G Jonah A Rainey, Kenneth A Bradley
1McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA.
Summary
Researchers discovered a second receptor, CMG2, for anthrax toxin protective antigen (PA). This finding identifies a new target for developing anthrax antitoxins and understanding disease pathogenesis.
Area of Science:
- Microbiology
- Toxicology
- Molecular Biology
Background:
- Bacillus anthracis secretes toxins crucial for anthrax pathogenesis.
- Protective Antigen (PA) binds to cell-surface receptors, initiating intoxication.
- Tumor Endothelial Marker 8 (TEM8) was the known receptor for PA.
Purpose of the Study:
- To identify additional cell-surface receptors for anthrax toxin PA.
- To characterize the interaction between PA and potential new receptors.
- To explore therapeutic strategies targeting anthrax toxin entry.
Main Methods:
- Identified Capillary Morphogenesis Gene 2 (CMG2) as a novel PA receptor.
- Utilized recombinant proteins to study PA-CMG2 binding.
- Assessed toxin internalization and inhibition assays.
- Performed Northern blot analysis for CMG2 expression.
Main Results:
- CMG2 shares structural similarity with TEM8 and binds PA directly.
- CMG2 mediates PA-mediated toxin internalization.
- CMG2 is widely expressed in human tissues.
- A soluble CMG2 domain inhibits PA-mediated intoxication.
Conclusions:
- CMG2 is a second functional receptor for anthrax toxin PA.
- CMG2 plays a role in anthrax pathogenesis.
- Soluble CMG2 represents a potential therapeutic agent against anthrax.