Rossio and Yoshida reveal how cells control the location of the mitosis-regulating protein Cdc55.
Cdc55 is a key component of the protein phosphatase 2A (PP2A) complex, which helps determine when cells begin and end mitosis. Two other proteins, Zds1 and Zds2, keep the complex under control. They switch on PP2A to nudge the cell into mitosis and switch it off to spur the cell to exit mitosis. Rossio and Yoshida wanted to investigate how this regulation occurs.
The researchers tracked the locations of Zds1, Zds2, and Cdc55 in budding yeast cells. Zds1 and Zds2 stayed exclusively in the cytoplasm, whereas Cdc55 could also enter the nucleus. To determine whether Cdc55's location altered its effect on mitosis, Rossio and Yoshida created mutant versions of the protein that remained either in the nucleus or the cytoplasm. Cells that harbored the cytoplasm-only Cdc55 form started mitosis normally, but yeast that made the exclusively nuclear version procrastinated, delaying the beginning of mitosis.
In the absence of Zds1 and Zds2, Cdc55 built up in the nucleus, where it prolonged mitosis by hindering the release of Cdc14, which normally helps push the cell into G1. The researchers think that Zds1 and Zds2 play a dual role. They trap Cdc55 in the cytoplasm, where it can prompt the cell to initiate mitosis. And because the proteins prevent Cdc55 from moving on to the nucleus, they allow the cell to exit mitosis.