The role of the polo-box of polo kinases, Plk and Cdc5, in cytokinesis.

Basic Sciences

Investigators

Abstract

Coordination of mitotic exit with timely initiation of cytokinesis is critical to ensure completion of mitotic events prior to cell division. The S. cerevisiae polo kinase Cdc5 functions in a pathway leading to the degradation of mitotic cyclin Clb2, thereby permitting mitotic exit. Here we provide evidence that Cdc5 also plays a role in regulating cytokinesis and that an intact polo-box, a conserved motif in the non-catalytic C-terminal domain of Cdc5, is required for this event. Depletion of Cdc5 function leads to an arrest in cytokinesis. Overexpression of the C-terminal domain of Cdc5 (cdc5DN), but not the corresponding polo-box mutant, resulted in connected cells. These cells shared cytoplasms with incomplete septa, and possessed aberrant septin ring structures. Provision of additional copies of endogeneous CDC5 remedied this phenotype, suggesting a dominant-negative inhibition of cytokinesis. The polo-box-dependent interactions between Cdc5 and septins (Cdc11 and Cdc12) and genetic interactions between the dominant-negative cdc5DN and Cyk2/Hof1 or Myo1 suggest that direct interactions between cdc5DN and septins resulted in inhibition of Cyk2/Hof1- and Myo1-mediated cytokinetic pathways. Thus, we propose that Cdc5 may coordinate mitotic exit with cytokinesis by participating in both APC activation and a polo-box-dependent cytokinetic pathway.