Neurabin-i is phosphorylated neuronal morphogenesis and by Cdk5: Implications for cortical migration
Neurabin-i is phosphorylated neuronal morphogenesis and by Cdk5: Implications for cortical migration
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DOI：
10.1091/mbc.e07-04-0372
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发表时间：
2007-11-01
影响因子：
3.3
通讯作者：
Nikolic, Margareta
中科院分区：
文献类型：
--
作者：
Causeret, Frederic;Jacobs, Tom;Nikolic, Margareta
神经元的正确形态和迁移对神经系统的正常发育至关重要，是通过细胞骨架元件的调节来实现的。我们发现神经元特异性f -肌动蛋白结合蛋白Neurabin-I在发育中的前脑中具有重要功能。我们发现，神经滨素- 1表达的增加和减少会影响神经元形态、神经突生长以及分化的皮质和海马神经元的径向迁移，这表明神经滨素- 1功能的严格调节是正常前脑发育所必需的。重要的是，Neurabin-I的缺失阻止锥体神经元迁移到大脑皮层，这表明它在皮质形成的早期阶段起着重要作用。我们证明在神经元中Rac1的激活受Neurabin-I表达水平的影响。此外，作为神经元迁移和形态的关键调节因子，Cdk5激酶可直接磷酸化Neurabin-I并控制其与F-actin的关联。Cdk5磷酸化位点的突变降低了Neurabin-I在体外和体内过表达的表型后果，这表明Neurabin-I的功能至少部分取决于其磷酸化状态。总之，我们的发现为前脑正常发育所需的f -肌动蛋白细胞骨架控制变化的信号通路提供了新的见解。
The correct morphology and migration of neurons, which is essential for the normal development of the nervous system, is enabled by the regulation of their cytoskeletal elements. We reveal that Neurabin-I, a neuronal-specific F-actin-binding protein, has an essential function in the developing forebrain. We show that gain and loss of Neurabin-I expression affect neuronal morphology, neurite outgrowth, and radial migration of differentiating cortical and hippocampal neurons, suggesting that tight regulation of Neurabin-I function is required for normal forebrain development. Importantly, loss of Neurabin-I prevents pyramidal neurons from migrating into the cerebral cortex, indicating its essential role during early stages of corticogenesis. We demonstrate that in neurons Rac1 activation is affected by the expression levels of Neurabin-I. Furthermore, the Cdk5 kinase, a key regulator of neuronal migration and morphology, directly phosphorylates Neurabin-I and controls its association with F-actin. Mutation of the Cdk5 phosphorylation site reduces the phenotypic consequences of Neurabin-I overexpression both in vitro and in vivo, suggesting that Neurabin-I function depends, at least in part, on its phosphorylation status. Together our findings provide new insight into the signaling pathways responsible for controlled changes of the F-actin cytoskeleton that are required for normal development of the forebrain.