Chromosome misalignment is associated with PLK1 activity at cenexin-positive mitotic centrosomes
Chromosome misalignment is associated with PLK1 activity at cenexin-positive mitotic centrosomes
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DOI：
10.1091/mbc.e18-12-0817
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发表时间：
2019-06-15
影响因子：
3.3
通讯作者：
Hehnly, Heidi
中科院分区：
文献类型：
--
作者：
Colicino, Erica G.;Stevens, Katrina;Hehnly, Heidi
有丝分裂激酶，polo样激酶1（PLK1），促进组装的两个有丝分裂纺锤体极，这是必要的微管为基础的纺锤体的形成，确保适当的染色体分布到两个形成的子细胞。纺锤体磁极的组成是不对称的。一个纺锤体极包含最古老的有丝分裂中心粒，即中心粒母体，中心粒母体附属蛋白和PLK1结合伴侣的大部分存在于此。我们假设PLK1活性在cenexin阳性的老年纺锤体极更大。我们的研究发现，PLK1不对称定位在纺锤体极点之间的条件下，染色体错位，染色体往往向最古老的纺锤体极点在cenexin和PLK1依赖的方式。在染色体错位期间，PLK1活性在最古老的纺锤体极特异性地增加，并且这种活性的增加在cenexin耗尽的细胞中丢失。我们提出了一个模型，PLK1活性升高，在中期最古老的纺锤体极的染色体错位。
The mitotic kinase, polo-like kinase 1 (PLK1), facilitates the assembly of the two mitotic spindle poles, which are required for the formation of the microtubule-based spindle that ensures appropriate chromosome distribution into the two forming daughter cells. Spindle poles are asymmetric in composition. One spindle pole contains the oldest mitotic centriole, the mother centriole, where the majority of cenexin, the mother centriole appendage protein and PLK1 binding partner, resides. We hypothesized that PLK1 activity is greater at the cenexin-positive older spindle pole. Our studies found that PLK1 asymmetrically localizes between spindle poles under conditions of chromosome misalignment, and chromosomes tend to misalign toward the oldest spindle pole in a cenexin- and PLK1-dependent manner. During chromosome misalignment, PLK1 activity is increased specifically at the oldest spindle pole, and this increase in activity is lost in cenexin-depleted cells. We propose a model where PLK1 activity elevates in response to misaligned chromosomes at the oldest spindle pole during metaphase.