Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast.

Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast.
复制标题

动力蛋白-8对有丝分裂微管动力学的影响有助于裂变酵母中的纺锤体功能。

DOI:
10.1091/mbc.e15-07-0505
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发表时间:
2016-11-07
影响因子:
3.3
通讯作者:
Betterton MD
Betterton MD
中科院分区:
生物学3区
文献类型:
--
作者:
Gergely ZR;Crapo A;Hough LE;McIntosh JR;Betterton MD

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在有丝分裂中,驱动蛋白-8运动蛋白破坏微管的稳定并增加染色体的丢失。在分裂酵母中,异常微管驱动的着丝点推动运动、三极性有丝分裂纺锤体和中期纺锤体长度的波动发生在激酶-8缺失突变体中。一个数学模型可以解释这些结果。运动蛋白8使微管不稳定。它们在细胞分裂过程中的缺失与有丝分裂染色体运动紊乱和染色体丢失有关。尽管最近研究了激酶-8对微管动力学的影响,但仍不清楚激酶-8有丝分裂表型是它们对微管动力学的影响、它们已建立的运动活性还是其他未知功能的结果。为了更好地了解激酶-8蛋白在有丝分裂中的作用,我们研究了裂变酵母激酶-8蛋白Klp5和Klp6缺失对染色体运动和纺锤体长度动力学的影响。微管驱动的着丝点推动运动和三极性有丝分裂纺锤体在缺乏Klp5而不缺乏Klp6的细胞中发生。激酶8缺失菌株在中期纺锤体长度波动较大,表明纺锤体长度稳定被破坏。光镜下的结果与数学模型的比较表明,驱动蛋白8对微管动力学、着丝点附着稳定性和纺锤体滑动力的影响可以解释染色体的异常运动和纺锤体长度的波动。
Kinesin-8 motor proteins destabilize microtubules and increase chromosome loss in mitosis. In fission yeast, aberrant microtubule-driven kinetochore pushing movements, tripolar mitotic spindles, and fluctuations in metaphase spindle length occurred in kinesin-8–deletion mutants. A mathematical model can explain these results. Kinesin-8 motor proteins destabilize microtubules. Their absence during cell division is associated with disorganized mitotic chromosome movements and chromosome loss. Despite recent work studying effects of kinesin-8s on microtubule dynamics, it remains unclear whether the kinesin-8 mitotic phenotypes are consequences of their effect on microtubule dynamics, their well-established motor activity, or additional, unknown functions. To better understand the role of kinesin-8 proteins in mitosis, we studied the effects of deletion of the fission yeast kinesin-8 proteins Klp5 and Klp6 on chromosome movements and spindle length dynamics. Aberrant microtubule-driven kinetochore pushing movements and tripolar mitotic spindles occurred in cells lacking Klp5 but not Klp6. Kinesin-8–deletion strains showed large fluctuations in metaphase spindle length, suggesting a disruption of spindle length stabilization. Comparison of our results from light microscopy with a mathematical model suggests that kinesin-8–induced effects on microtubule dynamics, kinetochore attachment stability, and sliding force in the spindle can explain the aberrant chromosome movements and spindle length fluctuations seen.