微管蛋白翻译后修饰对微管形成和神经元功能的作用及机制

项目名称： 微管蛋白翻译后修饰对微管形成和神经元功能的作用及机制

项目编号： No.31330046

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 鲍岚

作者单位： 中国科学院上海生命科学研究院

项目金额： 297万元

中文摘要： 微管蛋白包括α-tubulin和β-tubulin可以运用翻译后修饰影响微管的动力学、结构和功能。α-tubulin乙酰化的微管在神经系统高度富集，但其对微管动力学和神经元功能的影响和机制尚需深入研究。此外，神经系统中新的微管蛋白翻译后修饰和修饰酶有待发现。本项目将分析α-tubulin乙酰化修饰在神经元中对微管动力学和结构的影响；研究微管蛋白乙酰化修饰对于神经元迁移、生长、极性形成和轴树突发育的影响，揭示其作用的分子细胞机制；探讨α-tubulin乙酰化与神经退行性疾病的关系；寻找影响神经系统发育的新的微管蛋白翻译后修饰位点和修饰酶，研究其对微管形成以及神经元功能的调控作用和机制。本研究对微管蛋白调节微管形成的基本细胞生物学理论有贡献，为神经系统发育以及神经退行性疾病的发生发展提供新的分子和细胞机制，为治疗神经退行性疾病提供新策略。

中文关键词： 微管蛋白;翻译后修饰;微管;神经元;轴突生长

英文摘要： Tubulins including α-tubulins and β-tubulins adopt post-translational modification to affect microtubule dynamics, structure and function. The α-tubulin acetylation is highly enriched in nerve system. However, the effect and mechanism of α-tubulin acetylation on microtubule dynamics and neuronal function need to be further investigated. The novel post-translational modifications and modification enzymes of tubulins should be explored in nerve system. In the present project, we will analyze the effects of α-tubulin acetylation on microtubule dynamics and structure in neurons, study the effects of α-tubulin acetylation on neuronal migration, growth, polarity and axon/dendrite development, clarify the molecular and cellular mechanisms of these effects, and identify the relationship of α-tubulin acetylation with neurodegenerative diseases. We will search for novel post-translational modifications and modification enzymes of tubulins which play important roles in development of nerve system, and study their effects and regulatory mechanisms on microtubule formation and neuronal functions. Our study will contribute to basic theory of microtubule formation regulated by tubulins in Cell Biology, elucidate the molecular and cellular mechanisms for the development of nerve system and neurodegenerative diseases, and provide novel strategy for the treatment of neurodegenerative diseases.

英文关键词： Tubulin;Posttranslational modification;Microtubule;Neuron;Axon growth