Inhibition of cytokinesis by wiskostatin does not rely on N-WASP/Arp2/3 complex pathway.
BACKGROUND
Cytokinesis is the final step of cell division taking place at the end of mitosis during which the cytoplasmic content and replicated chromosomes of a cell are equally partitioned between the two daughter cells. This process is achieved by the formation and the ingression of an actomyosin contractile ring under the control of equatorial microtubules. The mechanisms of contractile ring formation are not fully understood but involve recruitment of preexisting actin filaments and de novo actin polymerisation.


RESULTS
In this study, we evaluated the role of the actin nucleation factor, Arp2/3 complex, during cytokinesis. We found that the Arp2/3 complex is recruited late to the cleavage furrow suggesting a potential involvement of Arp2/3 complex during this process. Furthermore, wiskostatin a potent inhibitor of N-WASP activity towards the Arp2/3 complex blocked cytokinesis without affecting mitosis. Nonetheless, this inhibition could not be reproduced using alternative approaches targeting the N-WASP/Arp2/3 complex pathway.


CONCLUSIONS
We conclude that the wiskostatin induced defective cytokinesis does not occur through the inhibition of the N-WASP/Arp2/3 pathway. Wiskostatin is likely to either directly target other proteins required for cytokinesis progression or alternately wiskostatin bound to N-WASP could affect the activity of other factors involved in cytokinesis.
Bompard
Guillaume
G
CRBM, CNRS UMR 5237, Université Montpellier I et II, 1919 route de Mende, 34293 Montpellier Cedex 5, France. guillaume.bompard@crbm.cnrs.fr
Rabeharivelo
Gabriel
G
Morin
Nathalie
N
D051376:Actin-Related Protein 2-3 Complex / Q000187:drug effects / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology*; D048749:Cytokinesis / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000187:drug effects / Q000502:physiology*
D051376:Actin-Related Protein 2-3 Complex; D002227:Carbazoles; D011412:Propanolamines; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C489942:wiskostatin; D015739:Nocodazole