Minus-End-Directed Kinesin-14 Motors Align Antiparallel Microtubules to Control Metaphase Spindle Length

• Published in: Developmental cell 2014-10, Vol.31 (1), p.61-72
• Main Authors: Hepperla, Austin J., Willey, Patrick T., Coombes, Courtney E., Schuster, Breanna M., Gerami-Nejad, Maryam, McClellan, Mark, Mukherjee, Soumya, Fox, Janet, Winey, Mark, Odde, David J., O’Toole, Eileen, Gardner, Melissa K.
• Format: Article
• Language: English
• Subjects: Kinesin - metabolism; Microtubule Proteins - metabolism; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Microtubules - ultrastructure; Models, Biological; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Spindle Apparatus - metabolism; Spindle Apparatus - ultrastructure
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.07.023

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-14 minus-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, in vitro 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. •Mitotic kinesin-14 motors align microtubules along the spindle axis during metaphase•Microtubules may be pivoted into spindle axis alignment by minus-end-directed motors•This allows kinesin-5 motors to efficiently exert outward microtubule sliding forces•Thus, a minus-end-directed motor can facilitate outwardly directed spindle forces Kinesin-14 motors align microtubules along the spindle axis to properly build a mitotic spindle, potentially by pivoting microtubules into alignment via their minus-end-directed motility. This then allows kinesin-5 motors to efficiently exert outward microtubule sliding forces. Thus, a minus-end-directed motor can facilitate outwardly directed spindle forces during mitosis.