Minus-end-directed kinesin-14 motors align antiparallel microtubules to control metaphase spindle length

Austin J. Hepperla, Patrick T. Willey, Courtney E. Coombes, Breanna M. Schuster, Maryam Gerami-Nejad, Mark McClellan, Soumya Mukherjee, Janet Fox, Mark Winey, David J. Odde, Eileen O'Toole, Melissa K. Gardner

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

During cell division, a microtubule-based mitotic spindle mediates the faithful segregation of duplicated chromosomes into daughter cells. Proper length control of the metaphase mitotic spindle is critical to this process and is thought to be achieved through a mechanism in which spindle pole separation forces from plus-end-directed motors are balanced by forces from minus-end-directed motors that pull spindle poles together. However, in contrast to this model, metaphase mitotic spindles with inactive kinesin-14minus-end-directed motors often have shorter spindle lengths, along with poorly aligned spindle microtubules. A mechanistic explanation for this paradox is unknown. Using computational modeling, invitro reconstitution, live-cell fluorescence microscopy, and electron microscopy, we now find that the budding yeast kinesin-14 molecular motor Kar3-Cik1 can efficiently align spindle microtubules along the spindle axis. This then allows plus-end-directed kinesin-5 motors to efficiently exert the outward microtubule sliding forces needed for proper spindle bipolarity.

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalDevelopmental Cell
Volume31
Issue number1
DOIs
StatePublished - Oct 13 2014

Bibliographical note

Funding Information:
M.K.G. is supported by the Pew Charitable Trusts through the Pew Scholars Program in the Biomedical Sciences and by NIH grant NIGMS GM-103833. The Boulder Laboratory for 3D EM of Cells is supported by grant P41GM103431-42 from NIGMS to Andreas Hoenger. D.J.O. is supported by NIH grant GM-071522. Parts of this work were carried out in the Characterization Facility, University of Minnesota, a member of the NSF-funded Materials Research Facilities Network ( http://www.mrfn.org ) via the MRSEC program.

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