RT Journal Article
SR Electronic
T1 Kinetochore-fiber lengths are maintained locally but coordinated globally by poles in the mammalian spindle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.26.517738
DO 10.1101/2022.11.26.517738
A1 Manuela Richter
A1 Lila Neahring
A1 Jinghui Tao
A1 Renaldo Sutanto
A1 Nathan H. Cho
A1 Sophie Dumont
YR 2022
UL http://biorxiv.org/content/early/2022/11/26/2022.11.26.517738.abstract
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.