title: The role of Hklp2 in the stabilization and maintenance of spindle bipolarity.
abstract: Spindle bipolarity relies on a fine balance of forces exerted by various molecular motors [1-4]. In most animal cells, spindle bipolarity requires sustained outward forces to push the spindle poles apart, an activity that is provided by Eg5, a conserved homotetrameric plus-end-directed kinesin that crosslinks and slides antiparallel microtubules apart [5]. These pushing forces are balanced by inward minus-end-directed forces. Impairing both Eg5 and dynein restores the formation of functional bipolar spindles [4], although the mechanism at play is far from clear. The current model also fails to explain why in some systems Eg5 inhibition does not promote bipolar spindle collapse [6, 7] or why increasing Eg5 levels does not interfere with bipolar spindle assembly [8]. Moreover, the C. elegans Eg5 ortholog is not required for bipolar spindle formation [9]. We show here that the kinesin Hklp2 participates in the assembly and stabilization of the bipolar spindle. Hklp2 localizes to the mitotic microtubules in a TPX2-dependent manner and to the chromosomes through Ki67. Our data indicate that its mechanism of action is clearly distinct from and complementary to that of Eg5, providing an additional understanding of the mechanism driving the formation and maintenance of the bipolar spindle.
authors.affiliation: Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Vanneste
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
authors.forename: Naoko
authors.initials: N
authors.lastname: Imamoto
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vernos
mesh_terms: D002460:Cell Line; D016764:Cell Polarity; D002877:Chromosomes, Human / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure
chemical_list: C486567:KIF15 protein, human; D016547:Kinesins