TPX2 promotes mitotic spindle formation by enhancing Eg5 accumulation on microtubules and limiting motor activity.

The kinesin Eg5 moves toward minus ends of astral microtubules in early mitosis, switching to plus-end motion in anaphase. Dynein is required for minus-end motion; depletion of TPX2 results in a switch to plus-end motion. On midzone microtubules, Eg5 moves in both directions. Our results explain the redistribution of Eg5 throughout mitosis.

Background: TPX2 is a mitotic microtubule-associated protein that regulates the kinesin, Eg5. Results: Full-length TPX2 is a more potent inhibitor of Eg5 velocity than truncated TPX2; differential regulation by TPX2 was not observed for monomeric Eg5. Conclusion: TPX2 inhibits Eg5 as a roadblock and by direct interaction with Eg5. Significance: TPX2 may contribute to the spatial and temporal regulation of the mitotic motor Eg5.

The mitotic spindle, a microtubule‐based structure, is required for chromosome segregation during cell division. Motor proteins are molecular machines that utilise the energy of adenosine triphosphate (ATP) hydrolysis to move along microtubules. During cell division, motor proteins are required for spindle formation, chromosome alignment and segregation. Thus, mitotic motor proteins are required for the cell to avoid aneuploidy, a hallmark of cancer. Key Concepts: Molecular motors, including dynein/dynactin and several families of kinesin, are required for mitosis. Kinesins contribute to establishing spindle bipolarity, positioning chromosomes between spindle poles and focusing spindle poles. Dynein contributes to the metaphase checkpoint, spindle positioning, regulating spindle length and pole focusing. To establish and maintain a mitotic spindle, motor proteins achieve a balance of forces on microtubules.

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