At the Right Time and at the Right Place: Control of Cytokinesis in Mammals

Ensuring that cytokinesis occurs at the right time and in the right place is essential to maintain euploidy and cell-cycle progression. Cytokinesis is triggered by the RhoA GEF Ect2, which localizes to the spindle midzone during anaphase and activates RhoA at the overlying cell cortex to stimulate contractile ring formation. Using a chemical inhibitor of the Polo kinase Plk1, Petronczki et al. (2007) showed that Plk1 is essential for cytokinesis, because it specifically promotes Ect2 localization and interaction with its midzone receptor HsCyk-4.I liked this paper for three reasons. As a biologist, I was impressed because the paper explains an important part of biology: how a cell-cycle kinase determines when and where cytokinesis occurs. As a geneticist, I appreciate a “tight allele.” The paper is a beautiful example of the power of chemical genetics to specifically and rapidly inhibit Polo at a specific cell-cycle stage. Finally, as a yeast cell-cycle researcher, it is always nice to see the dramatic conservation between yeast and mammals. In budding yeast, even though the bud neck and not the spindle midzone determines the site of cytokinesis, Polo kinase phosphorylates Rho GEFs to initiate contractile ring formation and cytokinesis.This PaperPick refers to “Polo-like Kinase 1 Triggers the Initiation of Cytokinesis in Human Cells by Promoting Recruitment of the RhoGEF Ect2 to the Central Spindle,” by M. Petronczki, M. Glotzer, N. Kraut, and J.-M. Peters, published in May 2007.Video AbstractHere, Jan-Michael Peters discusses the work as a collaboration between Mark Petronczki (in his group), Michael Glotzer of the University of Chicago, and Norbert Kraut of Boehringer Ingelheim, who provided the key reagent: BI 2536, a chemical inhibitor of Plk1. The authors would like to note that their work on the role of Plk1 in cytokinesis was inspired by early observations made in the laboratory of David Glover and that the research groups of Prasad Jallepalli (Sloan Kettering) and Aaron Straight (Stanford) have also identified Plk1 as a key regulator of cleavage furrow formation in mammalian cells