Coronin 2B介导的肌动蛋白动态变化调控神经元极性分化的分子机制研究

Neuronal polarization, characterized by the formation of a single axon and multiple dendrites, is an important process during early neuronal development. Reorganization of actin cytoskeleton is critical for neuritogenesis and further establishment of axon and dendrites in neurons. Mounting evidence suggests that a series of actin regulatory proteins are indispensable for neuronal axon/dendrites development. As an evolutionarily conserved actin regulatory protein family, coronins are capable of controlling many actin-dependent biological processes. Our previous work identified a neuronal-expressed coronin family protein, Coronin 2B, which regulates axon outgrowth in hippocampal neurons. By using primary culture of hippocampal neurons as neuronal differentiation model and in utero electroporation technique, we aim to systematically elucidate the role of Coronin 2B-driven actin dynamics during neuronal polarization. This study will shed light on the molecular mechanisms underlying neuronal polarization, and provide therapeutic clues for treating neuronal development dysfunction related diseases.

神经元的轴突和树突极性分化是神经元早期发育的重要过程。肌动蛋白细胞骨架的重构，对于神经突起的形成并进一步分化为轴突和树突非常关键。目前已发现许多细胞骨架调控蛋白对于神经元轴突和树突的发育过程是不可或缺的。Coronin蛋白家族是一类进化上保守的肌动蛋白调控蛋白，广泛参与多种依赖于肌动蛋白动态变化的生物过程。申请人的前期工作发现，一种Coronin家族成员Coronin 2B高度并特异性地表达于神经系统中，并调控神经元轴突生长。本项目拟在此基础上，利用原代培养的海马神经元自发分化模型与胚胎电转技术，从分子水平、细胞水平以及动物水平上系统地研究Coronin 2B介导的肌动蛋白细胞骨架动态变化对神经元极性分化的调控作用。本研究将增进我们对神经元极性分化机制的理解，并为今后治疗神经元发育异常引起的神经系统疾病提供新的治疗线索。