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ACD toxin–produced actin oligomers poison formin-controlled actin polymerization

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Science  31 Jul 2015:
Vol. 349, Issue 6247, pp. 535-539
DOI: 10.1126/science.aab4090

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A little toxin can do a lot

The actin cross-linking domain (ACD) is an actin-specific toxin produced by several bacterial pathogens. Heisler et al. discovered that ACD's pathogenic mechanism involves a highly unusual toxicity amplification cascade. Rather than directly inactivating the actin cytoskeleton, ACD blocks the activity of formins, actin regulatory proteins that play crucial roles in numerous cellular activities. ACD is exceptionally potent, even though its substrate is the most abundant protein of a eukaryotic cell: actin.

Science, this issue p. 535

Abstract

The actin cross-linking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin cross-linking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here, we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently “poisoned” the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by using actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.

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