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Expert
Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 8; Issue 7; 11 April 2006 Abstract
PDF
Current model for cellular intoxication by anthrax toxin
David J. Banks, Sabrina C. Ward and Kenneth A. Bradley
Figure 1. Current model
for cellular intoxication by anthrax toxin. Cellular
intoxication begins when protective antigen (PA) binds membrane-bound surface-exposed
anthrax toxin receptor (ANTXR). PA is secreted by Bacillus anthracis
as an 83 kDa monomer and is proteolytically processed either on the surface
of host cells or in the serum (Refs 123, 124)
to remove a 20 kDa fragment from the N-terminus. The remaining 63 kDa fragment
then heptamerises and binds the catalytic moieties lethal factor (LF) and oedema
factor (OF). Oligomerisation of PA induces clustering of ANTXRs, which drives
relocalisation into lipid rafts, resulting in dynamin- and clathrin-dependent
endocytosis and COP1-, ARAP3-, and ALIX-dependent trafficking of the toxin complex.
The endosome becomes acidified, causing the pre-pore structure to insert into
the membrane and thus form a pore. LF and OF are delivered to the cytosol through
the pore and act on host targets. LF inactivates MKKs/MEKs, promotes IL-8 mRNA
decay, and activates Nalp1b. Dashed lines indicate hypothetical or unknown interactions
during intoxication. Abbreviations: ALIX, apoptosis-linked gene 2 (ALG-2)-interacting
protein X; cAMP, cyclic AMP; ANTXR, anthrax toxin receptor; ARAP3, ankyrin repeat
and plekstrin homology domains-containing protein 3; H+S,
proton; IL-8, interleukin 8; MKK/MEK, kinase for MAPKs/ERKs (mitogen-activated
protein kinases or extracellular-signal-regulated kinases); PA, protective antigen.
Adapted from Ref. 44 (Copyright 2004), with permission from
Elsevier.
| References cited
in Figure 1
44 Sanchez, A.M. and Bradley, K.A. (2004) Anthrax toxin: can a little be a good thing? Trends Microbiol 12, 143-145, PubMed 123 Ezzell, J.W., Jr. and Abshire, T.G. (1992) Serum protease cleavage of Bacillus anthracis protective antigen. J Gen Microbiol 138, 543-549, PubMed 124 Panchal, R.G. et al. (2005) Purified Bacillus anthracis lethal toxin complex formed in vitro and during infection exhibits functional and biological activity. J Biol Chem 280, 10834-10839, PubMed |
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