The nuclear scaffold protein SAF-A is required for kinetochore-microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles
The nuclear scaffold protein SAF-A is required for kinetochore-microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles
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DOI：
10.1242/jcs.063347
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发表时间：
2011-02-01
影响因子：
4
通讯作者：
Fukui, Kiichi
中科院分区：
文献类型：
--
作者：
Ma, Nan;Matsunaga, Sachihiro;Fukui, Kiichi
细胞分裂时染色体的分离需要纺锤体的正确形成。在这里，我们表明，一个支架附着因子A（SAF-A），也被称为异质核核糖核蛋白-U，有助于附件的纺锤体微管（MTs）的着丝粒和纺锤体组织。在有丝分裂过程中，SAF-A定位于纺锤体、纺锤体中间区和胞质桥。RNA干扰导致的SAF-A缺失导致有丝分裂延迟以及染色体排列和纺锤体组装的缺陷。我们发现SAF-A与染色体外周蛋白核仁素和纺锤体调节因子Aurora-A和TPX 2特异性共免疫沉淀，表明SAF-A与核仁素和Aurora-A-TPX 2复合物相关。SAF-A与TPX 2和Aurora-A共定位于纺锤极和MT。从细胞中去除TPX 2或Aurora-A可消除SAF-A与有丝分裂纺锤体的结合。有趣的是，SAF-A可以与MT结合，并有助于Aurora-A靶向有丝分裂纺锤体MT。我们的研究结果表明，SAF-A是一种新的纺锤体调节剂，在运动舞蹈MT的附着和有丝分裂纺锤体组织中起着至关重要的作用。
Segregation of chromosomes during cell division requires correct formation of mitotic spindles. Here, we show that a scaffold attachment factor A (SAF-A), also known as heterogeneous nuclear ribonucleoprotein-U, contributes to the attachment of spindle microtubules (MTs) to kinetochores and spindle organization. During mitosis, SAF-A was localized at the spindles, spindle midzone and cytoplasmic bridge. Depletion of SAF-A by RNA interference induced mitotic delay and defects in chromosome alignment and spindle assembly. We found that SAF-A specifically co-immunoprecipitated with the chromosome peripheral protein nucleolin and the spindle regulators Aurora-A and TPX2, indicating that SAF-A is associated with nucleolin and the Aurora-A-TPX2 complex. SAF-A was colocalized with TPX2 and Aurora-A in spindle poles and MTs. Elimination of TPX2 or Aurora-A from cells abolished the association of SAF-A with the mitotic spindle. Interestingly, SAF-A can bind to MTs and contributes to the targeting of Aurora-A to mitotic spindle MTs. Our finding indicates that SAF-A is a novel spindle regulator that plays an essential role in kinetochore-MT attachment and mitotic spindle organization.