The Kinesin-13 Proteins Kif2a, Kif2b, and Kif2c/MCAK Have Distinct Roles during Mitosis in Human Cells
Open Access
- 1 August 2007
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 18 (8), 2970-2979
- https://doi.org/10.1091/mbc.e07-02-0110
Abstract
The human genome has three unique genes coding for kinesin-13 proteins called Kif2a, Kif2b, and MCAK (Kif2c). Kif2a and MCAK have documented roles in mitosis, but the function of Kif2b has not been defined. Here, we show that Kif2b is expressed at very low levels in cultured cells and that GFP-Kif2b localizes predominately to centrosomes and midbodies, but also to spindle microtubules and transiently to kinetochores. Kif2b-deficient cells assemble monopolar or disorganized spindles. Chromosomes in Kif2b-deficient cells show typical kinetochore-microtubule attachments, but the velocity of movement is reduced ∼80% compared with control cells. Some Kif2b-deficient cells attempt anaphase, but the cleavage furrow regresses and cytokinesis fails. Like Kif2a-deficient cells, bipolar spindle assembly can be restored to Kif2b-deficient cells by simultaneous deficiency of MCAK or Nuf2 or treatment with low doses of nocodazole. However, Kif2b-deficient cells are unique in that they assemble bipolar spindles when the pole focusing activities of NuMA and HSET are perturbed. These data demonstrate that Kif2b function is required for spindle assembly and chromosome movement and that the microtubule depolymerase activities of Kif2a, Kif2b, and MCAK fulfill distinct functions during mitosis in human cells.Keywords
This publication has 53 references indexed in Scilit:
- The Interplay of the N- and C-Terminal Domains of MCAK Control Microtubule Depolymerization Activity and Spindle AssemblyMolecular Biology of the Cell, 2007
- Kinesin-13s form rings around microtubulesThe Journal of cell biology, 2006
- Mammalian CLASP1 and CLASP2 Cooperate to Ensure Mitotic Fidelity by Regulating Spindle and Kinetochore FunctionMolecular Biology of the Cell, 2006
- Kinetochores Use a Novel Mechanism for Coordinating the Dynamics of Individual MicrotubulesCurrent Biology, 2006
- Efficient Mitosis in Human Cells Lacking Poleward Microtubule FluxCurrent Biology, 2005
- Functional Analysis of Human Microtubule-based Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA InterferenceMolecular Biology of the Cell, 2005
- Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle polesThe Journal of cell biology, 2004
- The KinI kinesin Kif2a is required for bipolar spindle assembly through a functional relationship with MCAKThe Journal of cell biology, 2004
- Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extractsNature, 1996
- Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends.The Journal of cell biology, 1987