The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.
The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.
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DOI：
10.1091/mbc.e15-02-0113
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发表时间：
2015-10-01
影响因子：
3.3
通讯作者：
Griffis ER
中科院分区：
文献类型：
--
作者：
Carvalhal S;Ribeiro SA;Arocena M;Kasciukovic T;Temme A;Koehler K;Huebner A;Griffis ER
在aaa综合征患者中发生突变的核孔蛋白ALADIN对于纺锤体的形成是必要的。没有阿拉丁，活跃的极光A会离开中心体。活跃极光A的重新定位导致特定纺锤体组装因子的重新分配，使纺锤体不稳定并减缓其形成。有丝分裂纺锤体的形成是一个复杂的过程，需要大量的细胞重组。有丝分裂激酶的调控控制着整个过程。其中一个有丝分裂控制者是极光A激酶，它本身受到高度调控。在这项研究中，我们发现核孔蛋白ALADIN是Aurora a的一个新的空间调节因子，如果没有ALADIN， Aurora a就会从中心体扩散到纺锤体微管上，从而影响微管调节因子亚群的分布，减缓纺锤体组装和染色体排列。ALADIN与不活跃的Aurora A相互作用，并在Aurora A抑制后被招募到纺锤极。有趣的是，ALADIN的突变会导致aaa综合征。我们发现，我们在ALADIN缺失后观察到的一些有丝分裂表型也发生在aaa综合征患者的细胞中，这提出了有丝分裂错误可能是该综合征的部分病因的可能性。
The nucleoporin ALADIN, which is mutated in patients with triple A syndrome, is necessary for proper spindle formation. Without ALADIN, active Aurora A moves away from centrosomes. The relocalization of active Aurora A leads to a redistribution of specific spindle assembly factors that make spindles less stable and slows their formation. The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome.