The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin.

Forces produced by motor proteins and microtubule dynamics within the mitotic spindle are crucial for proper chromosome segregation. In addition to linear forces, rotational forces or torques are present in the spindle, which are reflected in the left-handed twisted shapes of microtubule bundles that make the spindle chiral. However, the biological role and molecular origins of spindle chirality are unknown.

Microtubule-sliding modules based on kinesins EG5 and PRC1-dependent KIF4A drive human spindle elongation.

Proper chromosome segregation into two future daughter cells requires the mitotic spindle to elongate in anaphase. However, although some candidate proteins are implicated in this process, the molecular mechanism that drives spindle elongation in human cells is unknown. Using combined depletion and inactivation assays together with CRISPR technology to explore redundancy between multiple targets, we discovered that the force-generating mechanism of spindle elongation consists of EG5/kinesin-5 together with the PRC1-dependent motor KIF4A/kinesin-4, with contribution from kinesin-6 and kinesin-8.

Expansion microscopy of the mitotic spindle.

The mitotic spindle is a dynamic and complex cellular structure made of microtubules and associated proteins. Although the general localization of most proteins has been identified, the arrangement of the microtubules in the mitotic spindle and precise localization of various proteins are still under intensive research. However, techniques used previously to decipher such puzzles are resolution limited or require complex microscopy systems.