APC/CCdc20-mediated degradation of Clb4 prompts astral microtubule stabilization at anaphase onset

Zucca et al. identify in budding yeast two evolutionary conserved mitotic machineries, the Clb4-CDK1 and APC/C-Cdc20 complexes, as central regulators of astral microtubule dynamics. Key for accurate chromosome partitioning to the offspring is the ability of mitotic spindle microtubules to respond to different molecular signals and remodel their dynamics accordingly. Spindle microtubules are conventionally divided into three classes: kinetochore, interpolar, and astral microtubules (kMTs, iMTs, and aMTs, respectively). Among all, aMT regulation remains elusive. Here, we show that aMT dynamics are tightly regulated. aMTs remain unstable up to metaphase and are stabilized at anaphase onset. This switch in aMT dynamics, important for proper spindle orientation, specifically requires the degradation of the mitotic cyclin Clb4 by the Anaphase Promoting Complex bound to its activator subunit Cdc20 (APC/C-Cdc20). These data highlight a unique role for mitotic cyclin Clb4 in controlling aMT regulating factors, of which Kip2 is a prime candidate, provide a framework to understand aMT regulation in vertebrates, and uncover mechanistic principles of how the APC/C-Cdc20 choreographs the timing of late mitotic events by sequentially impacting on the three classes of spindle microtubules.

Automated summary

Zucca et al. identified the Clb4-CDK1 and APC/C-Cdc20 complexes as central regulators of astral microtubule dynamics in budding yeast. They found that astral microtubules are tightly regulated, with a switch in dynamics occurring at anaphase onset. The degradation of the mitotic cyclin Clb4 by APC/C-Cdc20 is crucial for this switch and plays a unique role in controlling factors involved in astral microtubule regulation.