Spatial Regulation of Kinetochore Microtubule Attachments by Destabilization at Spindle Poles in Meiosis I.
Spatial Regulation of Kinetochore Microtubule Attachments by Destabilization at Spindle Poles in Meiosis I.
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DOI：
10.1016/j.cub.2015.05.013
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发表时间：
2015-07-20
期刊：
影响因子：
--
通讯作者：
Lampson MA
中科院分区：
文献类型：
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作者：
Chmátal L;Yang K;Schultz RM;Lampson MA
为了确保细胞分裂过程中染色体的准确分离，错误的着丝点微管（MT）附着被识别并破坏。不适当的附件通常在动丝点之间缺乏张力，并且在纺锤上的位置偏离中心。低张力是一种被广泛接受的错误识别机制，但染色体位置是否调节MT附着一直难以测试。我们利用了一个减数分裂系统，在这个系统中，附着在相反纺锤杆上的着丝点与微管的相互作用不同，因此位置和张力可以解耦。在该系统中，在减数分裂I中，同源染色体在卵母细胞纺锤体上的位置偏离中心，而在正常张力下，由于具有不同着丝粒强度的小鼠品系杂交，表现为着丝粒蛋白水平不等。我们发现靠近纺锤极会破坏着丝酶- mt的稳定性，并且通过抑制纺锤极的Aurora A激酶可以恢复稳定的附着。在校正附着错误的过程中，着丝点mt在纺锤杆附近分离，以形成正确的附着。我们认为染色体在纺锤体上的位置为细胞分裂的保真度提供了空间线索。
To ensure accurate chromosome segregation in cell division, erroneous kinetochore-microtubule (MT) attachments are recognized and destabilized. Improper attachments typically lack tension between kinetochores and are positioned off-center on the spindle. Low tension is a widely accepted mechanism for recognizing errors, but whether chromosome position regulates MT attachments has been difficult to test. We exploited a meiotic system in which kinetochores attached to opposite spindle poles differ in their interactions with microtubules, and therefore position and tension can be uncoupled. In this system homologous chromosomes are positioned off-center on the spindle in oocytes in meiosis I, while under normal tension, as a result of crossing mouse strains with different centromere strengths, manifested by unequal kinetochore protein levels. We show that proximity to spindle poles destabilizes kinetochore-MTs, and that stable attachments are restored by inhibiting Aurora A kinase at spindle poles. During the correction of attachment errors, kinetochore MTs detach near spindle poles to allow formation of correct attachments. We propose that chromosome position on the spindle provides spatial cues for the fidelity of cell division.