Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity.

ABSTRACT: The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased vis

SUBMITTER: Moulding DA 

PROVIDER: S-EPMC4338607 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature