Effects of dynamin inactivation on pathways of anthrax toxin uptake

Werner Boll, Marcelo Ehrlich, R. John Collier, Tomas Kirchhausen

Research output: Contribution to journalArticlepeer-review

Abstract

Internalization and traffic to acidic endosomes of anthrax lethal factor (LF) and protective antigen (PA), bound to the anthrax toxin receptor (ATR), is required for LF translocation into the cytosol, where it can elicit its toxic effects. Dynamin is required for clathrin-mediated endocytosis, and long-term disruption of dynamin function blocks internalization of PA. We have used LFn-DTA, a surrogate of LF consisting of the N-terminal domain of LF fused to the catalytic subunit of diphtheria toxin, to differentiate the effects of acute and long-term block of dynamin function on LFn-DTA toxicity. Both forms of interference reduce LFn-DTA toxicity only partially, consistent with alternative routes for LFn-DTA endocytosis. In contrast, a long-term block of dynamin activity results in a further interference with LFn-DTA toxicity that is consistent with an altered endosomal environment, probably an increase in endosomal pH.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalEuropean Journal of Cell Biology
Volume83
Issue number6
DOIs
StatePublished - Jul 2004
Externally publishedYes

Keywords

  • Anthrax toxin
  • Clathrin
  • Dynamin
  • Endocytosis

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