The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment

被引:255
作者
Stumpff, Jason [1 ]
von Dassow, George [2 ]
Wagenbach, Michael [1 ]
Asbury, Charles [1 ]
Wordeman, Linda [1 ]
机构
[1] Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA
[2] Univ Washington, Friday Harbor Labs, Ctr Cell Dynam, Friday Harbor, WA 98250 USA
关键词
D O I
10.1016/j.devcel.2007.11.014
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During vertebrate cell division, chromosomes oscillate with periods of smooth motion interrupted by abrupt reversals in direction. These oscillations must be spatially constrained in order to align and segregate chromosomes with high fidelity, but the molecular mechanism for this activity is uncertain. We report here that the human kinesin-8 Kif18A has a primary role in the control of chromosome oscillations. Kif18A accumulates as a gradient on kinetochore microtubules in a manner dependent on its motor activity. Quantitative analyses of kinetochore movements reveal that Kif18A reduces the amplitude of preanaphase oscillations and slows poleward movement during anaphase. Thus, the microtubule-depolymerizing kinesin Kif18A has the unexpected function of suppressing chromosome movements. Based on these findings, we propose a molecular model in which Kif18A regulates kinetochore microtubule dynamics to control mitotic chromosome positioning.
引用
收藏
页码:252 / 262
页数:11
相关论文
共 36 条
  • [1] AULT JG, 1991, J CELL SCI, V99, P701
  • [2] MOVEMENT AND SEGREGATION OF KINETOCHORES EXPERIMENTALLY DETACHED FROM MAMMALIAN CHROMOSOMES
    BRINKLEY, BR
    ZINKOWSKI, RP
    MOLLON, WL
    DAVIS, FM
    PISEGNA, MA
    PERSHOUSE, M
    RAO, PN
    [J]. NATURE, 1988, 336 (6196) : 251 - 254
  • [3] Poleward tubulin flux in spindles: Regulation and function in mitotic cells
    Buster, Daniel W.
    Zhang, Dong
    Sharp, David J.
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (08) : 3094 - 3104
  • [4] A monomeric red fluorescent protein
    Campbell, RE
    Tour, O
    Palmer, AE
    Steinbach, PA
    Baird, GS
    Zacharias, DA
    Tsien, RY
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (12) : 7877 - 7882
  • [5] Inducing precocious anaphase in cultured mammalian cells
    Canman, JC
    Salmon, ED
    Fang, GW
    [J]. CELL MOTILITY AND THE CYTOSKELETON, 2002, 52 (02): : 61 - 65
  • [6] CASSIMERIS L, 1994, J CELL SCI, V107, P285
  • [7] Anaphase spindle mechanics prevent mis-segregation of merotelically oriented chromosomes
    Cimini, D
    Cameron, LA
    Salmon, ED
    [J]. CURRENT BIOLOGY, 2004, 14 (23) : 2149 - 2155
  • [8] Merotelic kinetochore orientation occurs frequently during early mitosis in mammalian tissue cells and error correction is achieved by two different mechanisms
    Cimini, D
    Moree, B
    Canman, JC
    Salmon, ED
    [J]. JOURNAL OF CELL SCIENCE, 2003, 116 (20) : 4213 - 4225
  • [9] The Drosophila kinesin-like protein KLP67A is essential for mitotic and male meiotic spindle assembly
    Gandhi, R
    Bonaccorsi, S
    Wentworth, D
    Doxsey, S
    Gatti, M
    Pereira, A
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (01) : 121 - 131
  • [10] Functional roles of poleward microtubule flux during mitosis
    Ganem, Neil J.
    Compton, Duane A.
    [J]. CELL CYCLE, 2006, 5 (05) : 481 - 485