Septin 14 is involved in cortical neuronal migration via interaction with Septin 4.

Septin 14 is involved in cortical neuronal migration via interaction with Septin 4.
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DOI:
10.1091/mbc.e09-10-0869
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发表时间:
2010-04-15
影响因子:
3.3
通讯作者:
Nagata K
Nagata K
中科院分区:
生物学3区
文献类型:
--
作者:
Shinoda T;Ito H;Sudo K;Iwamoto I;Morishita R;Nagata K

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Septins是一个保守的GTP/GDP结合蛋白家族,参与多种细胞功能。我们发现,敲除Septin 14或Septin 4导致皮质神经元迁移的抑制和有缺陷的前导过程形成。这些结果表明,一个新的功能septin在皮质发育。Septins是一个保守的三磷酸鸟苷/二磷酸鸟苷结合蛋白家族,涉及多种细胞功能,如细胞周期控制和胞质分裂。尽管septin家族的几个成员,包括Septin 14(Sept 14),在神经组织中大量表达,但对其生理功能,特别是在神经元发育中的作用知之甚少。在这里,我们报告说,Sept 14是强烈表达的皮质板发育中的大脑皮层。使用子宫内电穿孔方法进行的敲除实验表明,Sept 14的减少导致皮质神经元迁移的抑制。而编码RNA干扰抗性Sept 14的cDNA拯救了迁移缺陷,Sept 14的C-末端缺失突变体没有。生化分析表明,C-末端卷曲螺旋区的Sept 14与Septin 4(Sept 4)相互作用。敲除实验表明,Sept 4也参与体内皮质神经元迁移。此外,敲除Sept 14或Sept 4抑制迁移皮层神经元中的前导过程形成。这些结果表明,Sept 14通过与Sept 4相互作用参与大脑皮层神经元迁移。
Septins are a family of conserved GTP/GDP-binding proteins implicated in a variety of cellular functions. We found that knockdown of Septin 14 or Septin 4 resulted in inhibition of cortical neuronal migration and defective leading process formation. These results suggest a novel function of septin in cortical development. Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.
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发表时间: 2002-04-01
影响因子: 2.7
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