Published online 27 January 2003. doi:10.1083/jcb1603iti5
© The Rockefeller University Press,
0021-9525/2003/2/285-a $5.00
The Journal of Cell Biology, Volume 160, Number 3, 285-a-285
Anthrax toxin takes charge
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Multimerization of anthrax toxin (right) leads to raft association and uptake.
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Bacterial toxin proteins are generally thought to enter eukaryotic cells by passive hitchhiking, binding to a convenient receptor that is constitutively internalized by endocytosis to ensure their delivery to the cytoplasm. But on page 321, Abrami et al. show that, at least in the case of anthrax, the toxin precisely choreographs its uptake by hijacking a specific endocytic pathway. The work suggests a possible strategy for treating anthrax infections and also highlights a connection between raft-mediated and clathrin-dependent endocytosis, two pathways that were once considered to be mutually exclusive.
Bacillus anthracis produces a toxin with three subunits. After binding to the cellular anthrax toxin receptor, a transmembrane protein of unknown function, the protective antigen subunit undergoes cleavage and heptamerization and then binds to the lethal factor and edema factor subunits to carry the toxin proteins into the cell.
The authors found that cleaved, heptamerized protective antigen associates with lipid rafts, whereas the uncleaved protein does not. Artificially clustering the anthrax toxin receptor with an antibody sandwich also targets it to rafts and stimulates its endocytosis. Uptake of the receptor is both raft mediated and clathrin dependent. This latter finding dovetails with another recent report, which also demonstrated a connection between rafts and clathrin during endocytosis of the B cell receptor.
The results indicate that protective antigen, far from being a passive hitchhiker, actively initiates the clustering of a cell surface receptor, sending a signal that induces its uptake. This spatial reorganization of the receptor on the cell surface could be a promising target for novel therapies. 
Alan W. Dove
alanwdove{at}earthlink.net
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Anthrax toxin triggers endocytosis of its receptor via a lipid raft–mediated clathrin-dependent process
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