Disassembly of actin filaments by botulinum C₂ toxin and actin‐filament‐disrupting agents induces assembly of microtubules in human leukaemia cell lines

Abstract

Background information. C 2 toxin produced by Clostridium botulinum types C and D ADP-ribosylates actin monomers and inactivates their polymerization activities. The disassembly of actin filaments by C 2 toxin induces a polarization of cultured human leukaemia cell lines.Results. The polarization induced by C 2 toxin was temperature dependent and was prevented by nocodazole, a microtubule-disrupting agent, whereas it was promoted by paclitaxel, a microtubule-stabilizing agent. The fluorescence staining of polarized cells indicated an increase in microtubule assembly accompanying disassembly of actin filaments. Furthermore, several actin-filament-disrupting agents, other than C 2 toxin, also induced microtubule assembly and cell polarization, irrespective of their different mechanisms of action. The effects induced by some of the agents, which have lower binding affinities for actin, were reversible in response to the re-assembly of actin filaments.Conclusions. Thus the disassembly of actin filaments by C 2 toxin and actin-filament-disrupting agents induces assembly of microtubules followed by polarization of human leukaemia cell lines, indicating that the assembly/disassembly equilibrium of actin filaments influences the dynamics of microtubules, which control cell morphology and, in turn, diverse cellular processes.

The C2-streptavidin delivery system promotes the uptake of biotinylated molecules in macrophages and T-leukemia cells

“…Recent studies indicate that C2-toxin treatment at higher concentrations does not only result in actin depolymerization, but also triggers mictotubule-based polarization in HL-60 cells (Uematsu et al, 2007).…”

Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria

“…Increased bundling of microtubules was observed. Previously it was reported that the actin-ADP-ribosylating C2 toxin affects microtubule patterns in human leukemia cells by causing formation of microtubule bundles [40]. In addition actin filament-depolymerizing agents like cytochalasin and latrunculin, which directly interact with actin to interfere with actin polymerization, can induce microtubule-based cell surface extensions [41],[42].…”

ADP-Ribosylation and Cross-Linking of Actin by Bacterial Protein Toxins

“…However, it has been suggested that capture proteins like ACF7 and Clasp2, which are usually involved in stabilization of growing microtubules at the actin cell cortex, are mislocalized into the cytosol after toxin treatment, thereby losing the ability to capture growing microtubules (Schwan et al 2009). Changes in structure of microtubules induced by binary actindepolymerizing toxins have been also reported for leukemia cells (Uematsu et al 2007) but in this case, protrusion formation was not prominent. Role and functions of the protrusions, which form after partial depolymerization of F-actin, are not clear.…”