Cdc42 reactivation at growth sites is regulated by local cell-cycle-dependent loss of its GAP Rga4

Abstract

In fission yeast, polarized cell growth stops during division and resumes after cell separation. We uncoupled these sequential events by delaying cytokinesis with a temporary Latrunculin A treatment. Mitotic cells recovering from treatment initiate end growth without cell separation, displaying a polar elongation sans separation (PrESS) phenotype. PrESS cell ends reactivate Cdc42, a major regulator of polarized growth, before cell separation, but at a fixed time after anaphase B. A candidate screen implicates Rga4, a negative regulator of Cdc42, in this process. We show that Rga4 appears punctate at the cell sides during G2, but is diffuse during mitosis, extending to the ends. While the Morphogenesis Orb6 (MOR) pathway is known to promote cell separation and growth by activating protein synthesis, we find that for polarized growth, removal of Rga4 from the ends is also necessary. Therefore, we propose that growth resumes after division once the MOR pathway is activated and the ends lose Rga4 in a cell-cycle-dependent manner.