α-微管蛋白新型翻译后修饰SUMOylation在大脑皮层发育中的功能和作用机制研究

神经元极性建立和迁移是皮层发育的关键事件，是大脑皮层结构形成的基础。极性建立和迁移过程高度依赖微管动态的精确调控。因此，作为微管动态调控的重要方式，微管蛋白上的多种翻译后修饰在神经发育中发挥着关键作用。最近我们首次鉴定发现SUMOylation是α-微管蛋白的新型修饰，能够调节微管坍塌频率。然而该修饰在神经发育中的功能仍待研究。本项目将在体内和体外系统中，综合运用生化分离、形态分析和子宫内电转等多种技术，揭示α-微管蛋白SUMOylation在皮层发育期神经元极化和迁移中的作用，阐明该修饰在体外培养皮层神经元极性建立中的功能；解析该修饰对神经元微管动态性的影响，为体内和体外的功能表型提供机制解释。同时，试图探索大脑发育异常相关的α-微管蛋白突变对其SUMOylation的影响。本项目将为认识微管动态和皮层发育的翻译后修饰调控提供新的视角和思路。

Neuronal polarization and migration, which are crucial for lamination of cerebral cortex, are tightly regulated by microtubule cytoskeleton. Thus, proper microtubule dynamics are vital for brain development. Several post-translational modifications (PTM) on α- or β-tubulins, representing one of the mechanisms to modulate microtubule dynamics, have been found to be indispensable for cortical development. We recently reported that SUMOylation is a novel PTM on α-tubulin regulating MT catastrophe. Meanwhile, preliminary results of the present study showed that α-tubulin SUMOylation exists in neurons. However, its functions and working mechanisms in regulating neural development remain unclear. Here we will utilize different approaches including biochemical separation, morphological analysis and in utero electroporation to study the role of α-tubulin SUMOylation in polarization and migration during cortical development, and dissect the influence of SUMOylation on microtubule assembly and dynamics. In addition, we will also explore the relationship between α-tubulin SUMOylation and tubulinopathy-associated α-tubulin mutants. The study will provide a new perspective to understand the regulation of microtubule dynamics and cortical development by PTMs.