自噬通路如何特异有效靶向蛋白聚集体促进其清除是神经退行性疾病机制研究和自噬通路研究的一个核心问题。自噬接头蛋白CUET（Cue5 and Tollip）家族分子在我们最近研究中发现可以靶向泛素标记的蛋白聚集体进行自噬降解，有效保护细胞免受蛋白聚集体的细胞毒性。但是CUET家族分子是如何高效发挥其功能还是不清楚的。通过免疫沉淀－质谱技术，我们发现Cue5可以与细胞骨架微丝结合蛋白Lsb3相互作用，而且二者的相互作用对其发挥促进泛素蛋白聚集体的清除，保护细胞免受蛋白聚集体的细胞毒性是必需的。本课题将继续利用蛋白质相互作用分析、细胞存活检测、蛋白聚集体形成测定与静态和动态细胞内定位观察等技术，揭示CUET蛋白与细胞骨架微丝系统的相互作用及其在蛋白聚集体形成和自噬降解运送中的功能，深入阐明CUET作为自噬接头蛋白特异靶向清除泛素蛋白聚集体的分子机制。

Selective targeting of ubiquitylated substrates by autophagy is pivotal against cell toxicity cause by nerodegeneration disease related protein aggregates. Recently we found a conserved autophagy adaptor protein CUET（Cue5 and Tollip）family could efficiently recruit ubiquitylated protein aggregates for autophagic clearance. Here this project aims to further verify the mechanism of the CUET family. Based on immunoprecipitation-mass spectrometry data for Cue5 interacting proteins, we identified cytoskeleton actin binding protein Lsb3 as its binding partner. The interaction between Cue5 and Lsb3 is important for their role in helping cell clearance of ubiquitylated protein aggregates and protection from cell toxicity caused by protein aggregates such like huntingtin polyQ. Further research is planned to detect the role of Cue5-Lsb3 interaction in protein aggregate formation, transport and autophagic degradation.