KifC3 Promotes Mitotic Progression and Integrity of the Central Spindle in Cytokinesis

Abstract

Kinesin-14 motor proteins play a variety of roles during metaphase and anaphase. However, the functions of these motors in the dramatic changes in the mitotic spindle in the transition from telophase to cytokinesis are not known. We have identified the minus end directed motor, KifC3, as an important contributor to central bridge morphology at this stage. For the first time, we have localized KifC3 to the flanking regions of the central spindle in cytokinesis. When KifC3 function is perturbed, by expression of a dominant negative version of the protein, or by KifC3 knockdown, abscission is delayed, and there is an increase in the population of cells in telophase. Furthermore, KifC3's unique motor-dependent localization at the central bridge allows it to congress microtubules, promoting efficient progress through cytokinesis. Thus, the central bridge is both widened and extended upon perturbation of KifC3. Examination of KifC3 on growing microtubules in interphase indicated that it caps growing microtubules released from the centrosome during recovery from nocodazole treatment, highlighting its localization at microtubule minus ends. This microtubule capping occurs both in the region of the centrosome and in the cell periphery. In line with other Kinesin-14 family members, KifC3 may guide microtubules released from the centrosome to their destination at the bridge and/or may slide and crosslink central bridge microtubules in order to stage the cells for abscission.