PT  - JOURNAL ARTICLE
AU  - Manuela Richter
AU  - Lila Neahring
AU  - Jinghui Tao
AU  - Renaldo Sutanto
AU  - Nathan H. Cho
AU  - Sophie Dumont
TI  - Kinetochore-fiber lengths are maintained locally but coordinated globally by poles in the mammalian spindle
AID  - 10.1101/2022.11.26.517738
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.26.517738
4099  - http://biorxiv.org/content/early/2022/11/26/2022.11.26.517738.short
4100  - http://biorxiv.org/content/early/2022/11/26/2022.11.26.517738.full
AB  - At each cell division, nanometer-scale components self-organize to build a micron-scale spindle. In mammalian spindles, microtubule bundles called kinetochore-fibers attach to chromosomes and focus into spindle poles. Despite evidence suggesting that poles can set spindle length, their role remains poorly understood. In fact, many species do not have spindle poles. Here, we probe the pole’s contribution to mammalian spindle length, dynamics, and function by inhibiting dynein to generate spindles whose kinetochore-fibers do not focus into poles, yet maintain a metaphase steady-state length. We find that unfocused kinetochore-fibers have a mean length indistinguishable from control, but a broader length distribution, and reduced length coordination between sisters and neighbors. Further, we show that unfocused kinetochore-fibers, like control, can grow back to their steady-state length if acutely shortened by drug treatment or laser ablation: they recover their length by tuning their end dynamics, albeit slower due to their reduced baseline dynamics. Thus, kinetochore-fiber dynamics are regulated by their length, not just pole-focusing forces. Finally, we show that spindles with unfocused kinetochore-fibers can segregate chromosomes but fail to correctly do so. We propose that mammalian spindle length emerges locally from individual k-fibers while spindle poles globally coordinate k-fibers across space and time.Competing Interest StatementThe authors have declared no competing interest.