中华绒螯蟹Dscam基因的细胞吞噬调控机制研究

唐氏综合症细胞黏附分子（Dscam）对节肢动物细胞吞噬的调控已被广泛证实。但是，Dscam大量可变剪切亚型的病原特异性识别以及跨膜型和分泌型Dscam相互作用对吞噬的调控机理尚不明。基于我们的工作基础和前期研究结果，本项目拟从细菌特异性结合及蛋白协同作用层面阐明Dscam调控中华绒螯蟹血细胞吞噬的作用机理。具体内容包括：1）从抗原结合位点的角度聚类分析Dscam亚型的细菌特异性结合能力；2）明确跨膜型和分泌型Dscam共有细菌特异性结合功能及跨膜型Dscam独有细胞质尾对吞噬的调控模式；3）基于异源结合及同源亲和作用探索两种类型Dscam在细胞吞噬调控过程中的协同作用。以上研究将丰富对Dscam免疫功能的认识，并有助于更好的理解甲壳动物细胞吞噬的作用机理。

Dscam regulated phagocytosis has been widely confirmed in arthropod. However, phagocytic regulation mechanism of two significant characteristic that including huge alternative splicing Dscam isoforms inducing pathogens specific recognizing and protein-protein interaction between transmembrane and secreted Dscam are still largely unknown. Based on the preliminary results of our previous study, this project aim to uncover the mechanism of Dscam regulated phagocytosis in Chinese mitten crab via bacterial specific binding and protein synergistic effects. The research content includes: 1) analyze bacterial specific binding function of Dscam isoforms from the perspective of antigen binding sites; 2) define the different phagocytic regulation patterns of transmembrane and secreted Dscam shared bacterial specific binding and cytoplasmic tail that unique to transmembrane Dscam; 3) discover Dscam protein synergistic effects regulated phagocytosis based on pathogens and homophilic binding specificity. This study will enrich our knowledge of Dscam related immune functions, as well as benefit the understanding of phagocytic action mechanism in crustacean.