Abstract

Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP- over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends. KIF21B also contains a motor-inhibiting domain that does not fully block the interaction of the protein with microtubules, but rather enhances its pause-inducing activity by preventing KIF21B detachment from microtubule tips. Thus, KIF21B combines microtubule-binding and regulatory activities that together constitute an autonomous microtubule pausing factor.

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Author details

  1. Wilhelmina E van Riel

    Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Ankit Rai

    Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1569-0919
  3. Sarah Bianchi

    Biology and Chemistry, Paul Scherrer Institut, Villigen PSI, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Eugene A. Katrukha

    Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Qingyang Liu

    Cell Biology, Utrecht University, *Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Albert JR Heck

    Biomolecular Mass Spectrometry and Proteomics, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2405-4404
  7. Casper C Hoogenraad

    Utrecht University, *, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Michel O Steinmetz

    Biology and Chemistry, *Paul Scherrer Institut, *Villigen, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  9. Lukas C Kapitein

    Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9418-6739
  10. Anna Akhmanova

    Biology, Utrecht University, Utrecht, Netherlands
    For correspondence
    a.akhmanova@uu.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9048-8614

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (865.08.002)

  • Anna Akhmanova

European Research Council (609822)

  • Anna Akhmanova

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_138659)

  • Michel O Steinmetz

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (865.10.010)

  • Casper C Hoogenraad

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (711.011.005)

  • Albert JR Heck
  • Anna Akhmanova

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (184.032.201)

  • Albert JR Heck

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_166608)

  • Michel O Steinmetz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, van Riel et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Wilhelmina E van Riel
  2. Ankit Rai
  3. Sarah Bianchi
  4. Eugene A. Katrukha
  5. Qingyang Liu
  6. Albert JR Heck
  7. Casper C Hoogenraad
  8. Michel O Steinmetz
  9. Lukas C Kapitein
  10. Anna Akhmanova
(2017)
Kinesin-4 KIF21B is a potent microtubule pausing factor
eLife 6:e24746.
https://doi.org/10.7554/eLife.24746

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https://doi.org/10.7554/eLife.24746