title: Balanced activity of three mitotic motors is required for bipolar spindle assembly and chromosome segregation.
abstract: Bipolar spindle assembly requires force to organize the microtubule network. Here, we show that three motor proteins, namely Eg5, Kif15, and dynein, act together to produce the right force balance in the spindle. Excessive inward force results in monopolar spindle formation, while excessive outward force generation results in unstable spindles with splayed spindle poles. Blocking activity of all three motors prevents bipolar spindle formation, but established bipolar spindles are refractory to loss of all motor activity. Further analysis shows that although these preformed spindles remain bipolar, outward force generation is required to establish sufficient tension on kinetochores and to accomplish successful chromosome segregation. Together, these results show how Eg5, Kif15, and dynein work together to build a bipolar spindle and reveal an important role for antagonistic motors in chromosome segregation.
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Roy G H P
authors.initials: RG
authors.lastname: van Heesbeen
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Tanenbaum
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: r.medema@nki.nl.
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
mesh_terms: D045744:Cell Line, Tumor; D020090:Chromosome Segregation; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008938:Mitosis; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C470243:KIF11 protein, human; C486567:KIF15 protein, human; D004398:Dyneins; D016547:Kinesins