Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis

Cytokinesis terminates mitosis,resulting in separation of the two sister cells. septins,a conserved family of gtp-binding cytoskeletal proteins,are an absolute requirement for cytokinesis in budding yeast. we demonstrate that septindependence of mammalian cytokinesis differs greatly between cell types: genetic loss of the pivotal septin subunit sept7 in vivo reveals that septins are indispensable for cytokinesis in fibroblasts,but expendable in cells of the hematopoietic system. sept7-deficient mouse embryos fail to gastrulate,and septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic machinery,including hyperacetylation/stabilization of microtubules and stalled midbody abscission,leading to constitutive multinucleation. we identified the microtubule depolymerizing protein stathmin as a key molecule aiding in septin-independent cytokinesis,demonstrated that stathmin supplementation is sufficient to override cytokinesis failure in sept7-null fibroblasts,and that knockdown of stathmin makes proliferation of a hematopoietic cell line sensitive to the septin inhibitor forchlorfenuron. identification of septin-independent cytokinesis in the hematopoietic system could serve as a key to identify solid tumor-specific molecular targets for inhibition of cell proliferation. © 2014 menon et al.