Vacuole inheritance in the budding yeast Saccharomyces cerevisiae requires precise coordination between organelle transport and cell cycle progression. Central to this process is the vacuole adaptor protein Vac17, which binds myosin to mediate the transport of vacuoles to the daughter cell. The timely degradation of Vac17, essential for proper vacuole positioning, is regulated by the p21-activated kinase Cla4 and the E3 ubiquitin ligase Dma1. Previously, Ewald Hettema and colleagues implicated the spindle position checkpoint kinase Kin4, along with its functional paralogue Frk1, in the regulation of vacuole and peroxisome inheritance. Now, the same research group (Ekal et al., 2024) investigate the mechanism by which Kin4 functions. They find that Kin4 and Frk1 prevent Vac17 degradation in the mother cell and that double mutant (kin4Δfrk1Δ) cells display increased Vac17 turnover, leading to de novo vacuole formation in daughter cells, which is typically observed only when inheritance fails. Interestingly, deletion of CLA4 in kin4Δfrk1Δ cells restores vacuole transport to the bud, highlighting the opposing actions of Cla4 and Kin4 in the timely degradation of Vac17. Analogous to the zone model, which proposes that different Kin4 activity zones in mother and daughter regulate the spindle position checkpoint, the authors propose that Kin4 and Cla4 form distinct zones with antagonistic effects on Vac17 stability. Thus, this study not only uncovers a new role for Kin4 beyond cell cycle regulation but also provides new insights into the spatiotemporal regulation of organelle transport.
