轴突起始段（AIS）是神经元产生动作电位和维持细胞极性的关键区域，与神经元的形态、功能和疾病密切相关。目前对于AIS中蛋白质机器组装的了解十分有限，制约了相关的分子运作机制和致病机理的研究。巨型锚定蛋白ankyrin-G是构建AIS的核心支架蛋白，前期实验表明ankyrin-G的某些蛋白片段能在体外发生相变，并且其蛋白凝聚相具有富集离子通道蛋白的作用。由此我们推测ankyrin-G可能通过相变形成一个动态的蛋白质组装平台，参与AIS的发育调控和功能行使。本项目旨在验证这一猜想，将在体外全面考察锚定蛋白G的相变性质、研究此相变对AIS结构和功能的影响，并在此基础上探究该相变与相关疾病的联系。本项目将有助于理解AIS的组装和调控，为阐明AIS各项功能背后的分子机理奠定基础，也有助于启发其它超长无序蛋白的相关研究。

The axon initial segment (AIS) of neuron is an essential region for action potential generation and axon-dendrite polarity maintenance, and is closely related with neuron morphology, function and various diseases. Currently, studies about the working mechanisms of AIS and the molecular mechanisms underlying related diseases are largely restricted by the limited knowledge about the assembly of AIS protein machineries. Giant ankyrin-G is a key scaffold protein in organizing AIS. Our preliminary data show that giant ankyrin-G fragments could phase separate into protein condensates in vitro, and the condensates can enrich ion channel proteins. Thus, we speculate that giant ankyrin-G may form a dynamic protein assembly platform in AIS through protein phase transition, thereby contributing to AIS development, function and regulation. This project aims to verify the above-mentioned hypothesis. We will comprehensively characterize the ankyrin-G phase transition properties in vitro, investigate the effects of ankyrin-G phase transition on AIS structure and function, then study the relationship between phase transition and AIS related diseases. This project will promote our understanding of AIS assembly and regulation, and lay the foundation for further elucidation of the molecular mechanisms behind AIS functions. Also, this project could helps to inspire other studies on long intrinsically disordered proteins.