Cdk5 phosphorylates and stabilizes p27kip1 contributing to actin organization and cortical neuronal migration
Cdk5 phosphorylates and stabilizes p27kip1 contributing to actin organization and cortical neuronal migration
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DOI：
10.1038/ncb1338
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发表时间：
2006-01-01
影响因子：
21.3
通讯作者：
Hoshino, M
中科院分区：
文献类型：
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作者：
Kawauchi, T;Chihama, K;Hoshino, M
p（27 kip 1）是细胞周期蛋白依赖性激酶（CDK）抑制剂（CKI），通常抑制增殖细胞中的CDK活性。尽管最近在体外已经提出了p27在细胞迁移中的另一个作用，但是p27在细胞迁移中的生理重要性仍然是难以捉摸的，因为p27缺陷小鼠没有显示出任何明显的迁移缺陷相关表型.在这里，我们表明，Cdk 5，一种非常规的神经元CDK，磷酸化和稳定p27作为上游调节剂，维持有丝分裂后神经元中p27的量。体内RNA干扰（RNAi）实验表明，减少量的p27引起皮质神经元迁移的抑制，并减少迁移神经元过程中的F-肌动蛋白的量。Cdk 5 p27途径激活肌动蛋白结合蛋白，cofilin，其也显示参与体内皮质神经元迁移。我们的研究结果揭示了一个以前未知的新的关系CDK和CKI在GO-停滞的细胞，调节细胞骨架重组和神经元迁移在皮质生成。
p(27kip1), a cyclin- dependent kinase ( CDK) inhibitor ( CKI), generally suppresses CDK activity in proliferating cells. Although another role of p27 in cell migration has been recently suggested in vitro, the physiological importance of p27 in cell migration remains elusive, as p27- deficient mice have not shown any obvious migration- defect- related phenotypes. Here, we show that Cdk5, an unconventional neuronal CDK, phosphorylates and stabilizes p27 as an upstream regulator, maintaining the amount of p27 in post- mitotic neurons. In vivo RNA interference ( RNAi) experiments showed that reduced amounts of p27 caused inhibition of cortical neuronal migration and decreased the amount of F- actin in the processes of migrating neurons. The Cdk5 p27 pathway activates an actin- binding protein, cofilin, which is also shown to be involved in cortical neuronal migration in vivo. Our findings shed light on a previously unknown new relationship between CDK and CKI in GO- arrested cells that regulates cytoskeletal reorganization and neuronal migration during corticogenesis.