Ganem Neil J, Upton Kristi, Compton Duane A
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Curr Biol. 2005 Oct 25;15(20):1827-32. doi: 10.1016/j.cub.2005.08.065.
Chromosome segregation relies on the dynamic properties of spindle microtubules (MTs). Poleward MT flux contributes to spindle dynamics through the disassembly of MT minus ends at spindle poles coupled to the continuous poleward transport of spindle MTs. Despite being conserved in metazoan cells, the function of flux remains controversial because flux rates differ widely in different cell types. In meiotic systems, the rate of flux nearly matches that of chromosome movement, but in mitotic systems, flux is significantly slower than chromosome movement. Here, we show that spindles in human mitotic cells depleted of the kinesin-13 proteins Kif2a and MCAK lack detectable flux and that such cells frequently fail to segregate all chromosomes appropriately at anaphase. Elimination of flux reduces poleward chromosome velocity approximately 20%, but does not hinder bipolar spindle assembly, chromosome alignment, or mitotic progression. Thus, mitosis proceeds efficiently in human cells lacking detectable poleward MT flux. These data demonstrate that in human cultured cells, kinetochores are sufficient to effectively power chromosome movement, leading us to speculate that flux is maintained in these cells to fulfill other functional roles such as error correction or kinetochore regulation.
染色体分离依赖于纺锤体微管(MTs)的动态特性。极向微管流通过纺锤体极处微管负端的解聚以及纺锤体微管持续的极向运输,对纺锤体动态变化产生影响。尽管在后生动物细胞中高度保守,但微管流的功能仍存在争议,因为不同细胞类型中的微管流速率差异很大。在减数分裂系统中,微管流速率几乎与染色体移动速率匹配,但在有丝分裂系统中,微管流比染色体移动明显要慢。在此,我们表明,在缺乏驱动蛋白13蛋白Kif2a和MCAK的人类有丝分裂细胞中,纺锤体缺乏可检测到的微管流变化,并且这些细胞在后期常常无法正确分离所有染色体。微管流的消除使染色体向极速度降低约20%,但并不妨碍双极纺锤体组装、染色体排列或有丝分裂进程。因此,在缺乏可检测到的极向微管流的人类细胞中,有丝分裂仍能高效进行。这些数据表明,在人类培养细胞中,动粒足以有效地驱动染色体移动,这使我们推测,在这些细胞中维持微管流是为了实现其他功能,如错误校正或动粒调节。