A new research paper based upon International collaboration between Takashi Toda’s group and the Francis Crick Institute (London, UK) was published in the Journal of Cell Science online. This work is partly supported by “Program For Fostering Globally Talented Research” JSPS grant (S2902/JPMX05S2900002). The first author Dr Corinne Pinder stayed in Takashi Toda’s laboratory in 2018 (January-May) to carry out this research project.
Corinne L. Pinder, Yuzy Matsuo, Sebastian P. Maurer and Takashi Toda
Kinesin-8 and TOG collaborate to limit spindle elongation from prophase to anaphase A for proper chromosome segregation
High-fidelity chromosome segregation relies on proper microtubule regulation. Kinesin-8 has been shown to destabilise microtubules to reduce metaphase spindle length and chromosome movements in multiple species. XMAP215/chTOG polymerases catalyse microtubule growth for spindle assembly, elongation and kinetochore-microtubule attachment. Understanding of their biochemical activity has advanced but little work directly addresses the functionality and interplay of these conserved factors. We utilised the synthetic lethality of fission yeast kinesin-8 (Klp5-Klp6) and XMAP215/chTOG (Dis1) to study their individual and overlapping roles. We found that the non-motor kinesin-8 tailbox is essential for mitotic function; mutation compromises plus-end-directed processivity. Klp5-Klp6 induces catastrophes to control microtubule length and surprisingly, Dis1 collaborates with kinesin-8 to slow spindle elongation. Together, they enforce a maximum spindle length for a viable metaphase-anaphase transition and limit elongation during anaphase A to prevent lagging chromatids. Our work provides mechanistic insight into how kinesin-8 negatively regulates microtubules and how this functionally overlaps with Dis1 and highlights the importance of spindle length control in mitosis.