Kinesin-4 KIF21B is a potent microtubule pausing factor
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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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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