Letter | Published:

The bidirectional depolymerizer MCAK generates force by disassembling both microtubule ends

Nature Cell Biology volume 13, pages 846852 (2011) | Download Citation

Abstract

During cell division the replicated chromosomes are segregated precisely towards the spindle poles1,2. Although many cellular processes involving motility require ATP-fuelled force generation by motor proteins, most models of the chromosome movement invoke the release of energy stored at strained (owing to GTP hydrolysis) plus ends of microtubules3,4. This energy is converted into chromosome movement through passive couplers5,6,7, whereas the role of molecular motors is limited to the regulation of microtubule dynamics. Here we report, that the microtubule-depolymerizing activity of MCAK (mitotic centromere-associated kinesin), the founding member of the kinesin-13 family, is accompanied by the generation of significant tension—remarkably, at both microtubule ends. An MCAK-decorated bead strongly attaches to the microtubule side, but readily slides along it in either direction under weak external loads and tightly captures and disassembles both microtubule ends. We show that the depolymerization force increases with the number of interacting MCAK molecules and is 1 pN per motor. These results provide a simple model for the generation of driving force and the regulation of chromosome segregation by the activity of MCAK at both kinetochores and spindle poles through a ‘side-sliding, end-catching’ mechanism.

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Acknowledgements

We thank K. Kinosita, Jr., for critical reading and comments. This work was supported by Grants-in-Aid for Specially Promoted Research, Scientific Research (S) and the Asia–Africa Science and Technology Strategic Cooperation Promotion Program, Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to S.I.). This work was also supported by a Start-up Grant-in-Aid for Young Scientists (to S.U.).

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Affiliations

  1. Department of Physics, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

    • Yusuke Oguchi
    • , Takashi Ohki
    • , Sergey V. Mikhailenko
    •  & Shin’ichi Ishiwata
  2. Advanced Technology Development Core, Brain Science Institute, RIKEN, Saitama 351-0198, Japan

    • Seiichi Uchimura
  3. Advanced Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan

    • Shin’ichi Ishiwata
  4. Waseda Bioscience Research Institute in Singapore (WABIOS), Singapore 138667, Republic of Singapore

    • Shin’ichi Ishiwata

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Contributions

Y.O. carried out the experiments and analysed the results. Y.O., S.V.M. and S.I. designed the experiments and wrote the manuscript. Y.O., S.U. and T.O. prepared DNA constructs and purified proteins. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Shin’ichi Ishiwata.

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DOI

https://doi.org/10.1038/ncb2256

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