MCAK facilitates chromosome movement by promoting kinetochore microtubule turnover.

MCAK facilitates chromosome movement by promoting kinetochore microtubule turnover.
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MCAK通过促进动力学微管营业额来促进染色体运动。

DOI:
10.1083/jcb.200707120
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发表时间:
2007-12-03
影响因子:
7.8
通讯作者:
von Dassow, George
von Dassow, George
中科院分区:
生物学1区
文献类型:
--
作者:
Wordeman, Linda;Wagenbach, Michael;von Dassow, George

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有丝分裂着丝粒相关驱动蛋白(MCAK)/Kif 2C是迄今为止发现的最有效的微管(MT)去稳定酶。然而,MCAK在着丝粒的功能仍然是机械难以捉摸的,因为从细胞质MCAK的MT动态的全球调节的干扰。在这项研究中,我们提出了MCAK嵌合体和突变体设计的目标着丝粒相关的MCAK的机制分析。实时成像显示,着丝粒相关的MCAK的耗尽大大降低了姐妹着丝粒之间的方向协调。姐妹着丝粒方向拮抗作用导致运动速度降低和张力增加。姐妹着丝粒似乎无法脱离动粒MT有效地响应振荡运动过程中的方向切换线索。这些作用通过将异位MCAK锚定到着丝粒而逆转。我们认为,MCAK增加了所有着丝粒的动粒MT的营业额,以协调姐妹着丝粒之间的方向转换,并促进顺利易位。这可能有助于染色体分离过程中的错误纠正,直接通过缓慢的MT周转或间接通过机械释放的MT在促进运动。
Mitotic centromere-associated kinesin (MCAK)/Kif2C is the most potent microtubule (MT)-destabilizing enzyme identified thus far. However, MCAK's function at the centromere has remained mechanistically elusive because of interference from cytoplasmic MCAK's global regulation of MT dynamics. In this study, we present MCAK chimeras and mutants designed to target centromere-associated MCAK for mechanistic analysis. Live imaging reveals that depletion of centromere-associated MCAK considerably decreases the directional coordination between sister kinetochores. Sister centromere directional antagonism results in decreased movement speed and increased tension. Sister centromeres appear unable to detach from kinetochore MTs efficiently in response to directional switching cues during oscillatory movement. These effects are reversed by anchoring ectopic MCAK to the centromere. We propose that MCAK increases the turnover of kinetochore MTs at all centromeres to coordinate directional switching between sister centromeres and facilitate smooth translocation. This may contribute to error correction during chromosome segregation either directly via slow MT turnover or indirectly by mechanical release of MTs during facilitated movement.
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发表时间: 1986-03
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