减数分裂I中纺锤体极处的动粒微管附着通过去稳定化进行空间调控。

Spatial Regulation of Kinetochore Microtubule Attachments by Destabilization at Spindle Poles in Meiosis I.

作者信息

Chmátal Lukáš, Yang Karren, Schultz Richard M, Lampson Michael A

机构信息

Department of Biology, University of Pennsylvania, 433 South University Avenue, Philadelphia, PA 19104, USA.

Department of Biology, University of Pennsylvania, 433 South University Avenue, Philadelphia, PA 19104, USA.

出版信息

Curr Biol. 2015 Jul 20;25(14):1835-41. doi: 10.1016/j.cub.2015.05.013. Epub 2015 Jul 9.

Abstract

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 MTs 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 inhibition of 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.

摘要

为确保细胞分裂过程中染色体的准确分离,错误的动粒-微管(MT)附着会被识别并使其不稳定。不正确的附着通常在动粒之间缺乏张力,并且在纺锤体上的位置偏离中心。低张力是一种广泛认可的错误识别机制,但染色体位置是否调节微管附着一直难以验证。我们利用了一种减数分裂系统,其中附着在相反纺锤体极上的动粒与微管的相互作用不同,因此位置和张力可以解耦。在这个系统中,由于将具有不同着丝粒强度的小鼠品系杂交,导致动粒蛋白水平不等,同源染色体在减数分裂I期的卵母细胞中位于纺锤体的偏心位置,而处于正常张力下。我们发现靠近纺锤体极会使动粒-微管不稳定,并且通过抑制纺锤体极处的极光激酶A可恢复稳定附着。在纠正附着错误的过程中,动粒-微管在纺锤体极附近脱离,以允许形成正确的附着。我们提出纺锤体上的染色体位置为细胞分裂的保真度提供了空间线索。

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