Abstract
Cytokinesis in animal cells involves the contraction of an actomyosin ring formed at the cleavage furrow. Nuclear division, or karyokinesis, must be precisely timed to occur before cytokinesis in order to prevent genetic anomalies that would result in either cell death or uncontrolled cell division. The septin family of GTPase proteins has been shown to be important for cytokinesis although little is known about their role during this process. Here we investigate the distribution and function of the mammalian septin MSF. We show that during interphase, MSF colocalizes with actin, microtubules, and another mammalian septin, Nedd5, and coprecipitates with six septin proteins. In addition, transfections of various MSF isoforms reveal that MSF-A specifically localizes with microtubules and that this localization is disrupted by nocodazole treatment. Furthermore, MSF isoforms localize primarily with tubulin at the central spindle during mitosis, whereas Nedd5 is mainly associated with actin. Microinjection of affinity-purified anti-MSF antibodies into synchronized cells, or depletion of MSF by small interfering RNAs, results in the accumulation of binucleated cells and in cells that have arrested during cytokinesis. These results reveal that MSF is required for the completion of cytokinesis and suggest a role that is distinct from that of Nedd5.