NuMA mechanically reinforces the spindle independently of its partner dynein

Summary of work: During cell division, both motor and non-motor proteins organize microtubules to build the spindle and maintain it against opposing forces. NuMA, a long microtubule-binding protein, is essential to spindle structure and function. NuMA recruits the motor dynein to actively cluster spindle microtubule minus-ends, but whether NuMA performs other spindle roles remains unknown. Here, we show that NuMA acts independently of dynein to passively reinforce the mammalian spindle. NuMA that cannot bind dynein is sufficient to protect spindle poles against fracture under external force. In contrast, NuMA with a shorter coiled-coil or disrupted self-interactions cannot protect spindle poles, and NuMA turnover differences cannot explain mechanical differences. In vitro, NuMA’s C-terminus self-interacts and bundles microtubules without dynein, dependent on residues essential to pole protection in vivo. Together, this suggests that NuMA reinforces spindle poles by crosslinking microtubules, using its long coiled-coiled and self-interactions to reach multiple, far-reaching pole microtubules. We propose that NuMA acts as a mechanical “multitasker” targeting contractile motor activity and separately crosslinking microtubules, both functions synergizing to drive spindle mechanical robustness.

Data associated with the paper: "NuMA mechanically reinforces the spindle independently of its partner dynein", Cho et al. Current Biology (DOI: https://doi.org/10.1016/j.cub.2025.07.028)

Here, we include data used to generate the figures in this paper. Files are created and can be opened with GraphPad Prism.