PQBP1调节脆性X智力迟滞蛋白FMR1功能的机制研究

智力发育迟滞是儿童中常见的神经发育疾病。遗传分析显示多聚谷氨酰胺结合蛋白（PQBP1)基因突变与智力发育迟滞密切相关。但分子功能和其致病机理目前还不完全清楚。文献报道显示PQBP1基因与脆性X综合症相关基因FMR1均定位于X染色体，且两者缺失或突变都会导致智力发育迟滞。我们前期研究结果显示两者具有相互作用，并具有类似的神经发育缺陷表型。在本项目中，我们将利用果蝇为模式生物，综合运用生物化学、细胞生物学、遗传学和神经生物学的方法，研究两者相互作用对FMR1分子功能的影响，阐明两者间的联系。为揭示PQBP1和FMR1的分子功能提供新思路。

Mental retardation (MR) is one of the most common neurodevelopmental diseases in children.Poly Q binding protein 1 (PQBP1) has been identified by genetic analysis as one of the disease causing genes for MR, but its function and pathological mechanism are still largely unknown.Studies have shown that PQBP1 is also located to X chromosome as Fragile X mental retardation protein FMR1, whose loss or mutations cause mental retardation. Our preliminary data show PQBP1 interacts with FMR1. Both dpqbp1 and dfmr1 mutant flies have the similar phenotypes of neurodevelopmental defects. In this proposal, we will utilize a combination of approaches, such as biochemistry, cell biology, genetics and neurobiology to study the interaction between PQBP1 and FMR1 in Drosophila models. We would like to investigate how PQBP1 regulates the FMR1 function, by which we can get a better understanding of the complex relationship between PQBP1 and FMR1, and shad light on their functional studies.