Disassembly of actin filaments by botulinum C2 toxin and actin-filament-disrupting agents induces assembly of microtubules in human leukaemia cell lines.
BACKGROUND
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.
Uematsu
Yosuke
Y
Department of Veterinary Medicine, Nippon Veterinary and Life Science University, Kyonan 1-7-1, Musashino, Tokyo 180-8602, Japan.
Kogo
Yasusi
Y
Ohishi
Iwao
I
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D050257:Tubulin Modulators / Q000494:pharmacology
D000199:Actins; D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D001905:Botulinum Toxins; C096324:botulinum toxin type C; D017239:Paclitaxel; D015739:Nocodazole