The Rho GTPase Cdc42 is a central regulator of polarised growth in fission yeast. Cdc42 is inactivated during early mitosis, which leads to the shutdown of cell growth, but how growth resumes after the completion of cell division is not entirely clear. Now, Maitreyi Das and colleagues (Rich-Robinson et al., 2021) investigate this question by first testing whether cytokinesis and subsequent cell separation impact the timing of polarised cell growth initiation and Cdc42 reactivation. Surprisingly, they report that this is not the case, as artificially delaying cytokinesis with the drug Latrunculin A uncouples cell growth and division, resulting in a polar elongation simultaneous with septation (PrESS) phenotype wherein cells that are treated in mitosis resume growth as they form a septum. Moreover, Cdc42 activity resumes at a fixed time after anaphase B in PrESS cells, which further suggests that the timing of growth reactivation occurs in response to a mitotic cue. The authors then carry out a candidate screen for cell-cycle-dependent regulators of Cdc42 and identify the Cdc42 GAP Rga4. Rga4 localises to cell sides during G2 and extends to cell ends – the future growth sites – during mitosis, from where it is subsequently lost following cell division. Collectively, these data support a model where Cdc42 reactivation at growth sites is regulated by the cell-cycle-dependent removal of its inactivator Rga4.
