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Kinesin-8 and Dis1/TOG collaborate to limit spindle elongation from prophase to anaphase A for proper chromosome segregation in fission yeast.

J. Cell. Sci.2019 Sep 23;132(18)
Corinne Pinder 1 , Yuzy Matsuo 2 , Sebastian P Maurer 3 , Takashi Toda 4
Corinne Pinder 1 , Yuzy Matsuo 2 , Sebastian P Maurer 3 , Takashi Toda 4

[No authors listed]

Author information
  • 1 Division of Biological and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan.
  • 2 Synthetic and Systems Biochemistry of the Microtubule Cytoskeleton Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 3 Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
  • 4 Hiroshima Research Center for Healthy Aging (HiHA), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan.

摘要


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. © 2019. Published by The Company of Biologists Ltd.

KEYWORDS: Fission yeast, Kinesin-8, Microtubules, Spindle elongation, XMAP215/TOG