NDEL1 phosphorylation by aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment
NDEL1 phosphorylation by aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment
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DOI：
10.1128/mcb.00878-06
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Hirotsune, Shinji
中科院分区：
文献类型：
--
作者：
Mori, Daisuke;Yano, Yoshihisa;Hirotsune, Shinji
NDEL 1是LIS 1的结合伴侣，其在有丝分裂细胞分裂和神经元迁移期间参与细胞质动力蛋白功能和微管组织的调节。NDEL 1优先定位于中心体，是细胞周期激活激酶（包括CDK 1）的可能靶点。特别是，NDEL 1通过CDK 1磷酸化促进katanin p60募集到中心体并触发微管重塑。在这里，我们表明Aurora-A在有丝分裂进入开始时在Ser 251处磷酸化NDEL 1。有趣的是，极光-A磷酸化的NDEL 1迅速下调，此后通过泛素化介导的蛋白质降解。此外，NDEL 1是通过与TACC 3相互作用靶向TACC 3的中心体所必需的。NDEL 1的Aurora-A磷酸化模拟突变体的表达有效地挽救了Aurora-A缺失细胞的中心体成熟和分离缺陷。我们的研究结果表明，Aurora-A介导的NDEL 1磷酸化对于中心体分离和中心体成熟以及有丝分裂进入至关重要。
NDEL1 is a binding partner of LIS1 that participates in the regulation of cytoplasmic dynein function and microtubule organization during mitotic cell division and neuronal migration. NDEL1 preferentially localizes to the centrosome and is a likely target for cell cycle-activated kinases, including CDK1. In particular, NDEL1 phosphorylation by CDK1 facilitates katanin p60 recruitment to the centrosome and triggers microtubule remodeling. Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. In addition, NDEL1 is required for centrosome targeting of TACC3 through the interaction with TACC3. The expression of Aurora-A phosphorylation-mimetic mutants of NDEL1 efficiently rescued the defects of centrosomal maturation and separation which are characteristic of Aurora-A-depleted cells. Our findings suggest that Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry.