The negatively charged carboxy-terminal tail of β-tubulin promotes proper chromosome segregation.
The negatively charged carboxy-terminal tail of β-tubulin promotes proper chromosome segregation.
复制标题
β-微管蛋白带负电荷的羧基末端尾部促进适当的染色体分离。
DOI：
10.1091/mbc.e15-05-0300
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发表时间：
2016
影响因子：
3.3
通讯作者：
Moore,JeffreyK
中科院分区：
文献类型：
--
作者：
Fees,ColbyP;Aiken,Jayne;O'Toole,EileenT;GiddingsJr,ThomasH;Moore,JeffreyK
尽管微管在染色体分离中具有广泛保守的作用，但我们对微管蛋白的分子特征如何影响其潜在机制的了解有限。在这里，我们研究了α-和β-微管蛋白的带负电的羧基末端结构域(CTT)，使用了一系列改变或去除萌芽酵母中CTT的突变体。我们发现，消融β-CTT会导致染色体损失率和细胞周期延迟增加。互补的活细胞成像和电子断层扫描表明，β-CTT对于正确定位动心和组织组装纺锤体内的微管是必要的。我们确定了一个带负电荷的氨基酸的最小区域，这是适当的染色体分离所必需的和充分的，并提供了这一功能可能在不同物种之间保守的证据。我们的结果首次在体内提供了微管蛋白CTTS在染色体分离中的特定作用的证据。我们认为，β-CTT通过稳定纺锤体和促进染色体向纺锤体两极移动的力来促进染色体的有序分离。
Despite the broadly conserved role of microtubules in chromosome segregation, we have a limited understanding of how molecular features of tubulin proteins contribute to the underlying mechanisms. Here we investigate the negatively charged carboxy-terminal tail domains (CTTs) of α- and β-tubulins, using a series of mutants that alter or ablate CTTs in budding yeast. We find that ablating β-CTT causes elevated rates of chromosome loss and cell cycle delay. Complementary live-cell imaging and electron tomography show that β-CTT is necessary to properly position kinetochores and organize microtubules within the assembling spindle. We identify a minimal region of negatively charged amino acids that is necessary and sufficient for proper chromosome segregation and provide evidence that this function may be conserved across species. Our results provide the first in vivo evidence of a specific role for tubulin CTTs in chromosome segregation. We propose that β-CTT promotes the ordered segregation of chromosomes by stabilizing the spindle and contributing to forces that move chromosomes toward the spindle poles.