Department of Molecular Neurobiology, Aichi Human Service Center, Institute for Developmental Research, Kasugai, Aichi 480-0392, Japan.
Mol Biol Cell. 2010 Apr 15;21(8):1324-34. doi: 10.1091/mbc.e09-10-0869. Epub 2010 Feb 24.
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.
septin 是一类保守的鸟嘌呤三磷酸/鸟嘌呤二磷酸结合蛋白，参与多种细胞功能，如细胞周期调控和胞质分裂。尽管 septin 家族的几个成员，包括 Septin 14（Sept14），在神经组织中大量表达，但它们的生理功能知之甚少，特别是在神经元发育方面。在这里，我们报告说 Sept14 在大脑皮质发育中的皮质板中强烈表达。通过体内电穿孔的方法进行的 knockdown 实验表明，降低 Sept14 的表达会抑制皮质神经元的迁移。然而，编码 RNA 干扰抗性 Sept14 的 cDNA 拯救了迁移缺陷，而 Sept14 的 C 末端缺失突变体则没有。生化分析表明，Sept14 的 C 末端卷曲螺旋区与 Septin 4（Sept4）相互作用。knockdown 实验表明，Sept4 也参与体内皮质神经元的迁移。此外，降低 Sept14 或 Sept4 的表达会抑制迁移皮质神经元的前导过程形成。这些结果表明，Sept14 通过与 Sept4 的相互作用参与大脑皮质中的神经元迁移。
