Aha1基因对斑马鱼肌小节组装的调控作用

肌小节组装是复杂而高度有序的过程，与肌营养不良、肌无力等肌原性肌病的发生发展及治疗密切相关。肌小节组装需要分子伴侣协助，伴侣蛋白Hsp90和UNC45在其中非常重要。Aha1能显著增强Hsp90的ATP酶活性，促进Hsp90构象改变与顾客蛋白结合。目前Aha1与Hsp90相互作用关系的报道采用生化技术，细胞或原生动物模型开展，在脊椎动物中缺乏相关研究。Aha1在斑马鱼骨骼肌中有特异性表达，且未见Aha1调控肌小节组装方面的报道，我们已经克隆Aha1基因并获得斑马鱼突变体。在此基础上，采用遗传学手段干扰Aha1的表达，分析斑马鱼运动能力、肌小节蛋白、Hsp90和UNC45的变化；通过结构域敲除，定点突变和免疫共沉淀技术确定Aha1调控肌小节组装的结构域，揭示肌小节组装中Aha1与 Hsp90、UNC45相互关系，加深对脊椎动物肌小节组装过程的认识，为肌原性肌病的诊治奠定重要的理论和实验基础。

Sarcomere assembly, a highly orchestrated affair, is associated with the development and treatment of muscle original myopathy such as muscular dystrophy and muscle weakness. Chaperones play an important role in assisting sarcomeric protein folding, assembly and maintenance sarcomere stability, especial for Hsp90. It was found that aha1, the activator of hsp90 ATPase 1, had specific expression in zebrafish skeletal muscle. Zebrafish has more advanges on studying sacomere assembly than other vetebrate models. We will detect the time and space expression of aha1 during zebrafish development using in situ hybridation, analyse the phenotype of sacomere and abundance of sarcomeric proteins after disturbing the expression of aha1. In addition, the key domain and amino acid in regulationg sarcomere assembly will be found by aha1 gene deletion and site-specific mutation. The results of the program will help us to know more about sarcomere assembly and provide information for myopathy diagnose and treatment.