中华绒螯蟹Dscam蛋白特异性调控细胞吞噬的机制研究

可变剪接普遍存在于真核生物中，是基因表达调控的重要环节。唐氏综合症细胞黏附分子（Dscam）是可变剪接的代表性基因，在节肢动物中可潜在产生几万种异构体，并与特异性免疫反应密切相关。我们的前期研究发现，中华绒螯蟹Dscam基因可潜在产生30,600种异构体，分泌型Dscam通过病原结合表位特异性结合细菌后以同源亲和作用结合特定跨膜型Dscam为受体调控血细胞吞噬功能。但是，分泌型Dscam与细菌特异性结合的分子机理以及通过细胞膜表面受体调控吞噬的作用机制仍极不清楚。为此，本项目将筛选分泌型Dscam特异性结合细菌的靶标，明确细菌结合分泌型Dscam病原结合表位的核心氨基酸区域，建立跨膜型Dscam调控细胞吞噬的信号转导途径，探索分泌型Dscam调控细胞吞噬的其他细胞膜表面受体。上述研究将揭示Dscam蛋白特异性调控细胞吞噬的作用机制，为阐释该蟹乃至其他甲壳动物的抗菌机理提供重要的科学依据。

Alternative splicing has been widely found in eukaryotes, which has a critical role in regulating gene expression. Dscam is a representative gene in alternative splicing, which may generate more than 10 thousand alternatively spliced isoforms in the arthropod, and its function in specific immunity has been reported. Our preliminary studies found Dscam may potentially generate 30,600 isoforms through alternative splicing, secreted Dscam can regulate phagocytosis via specific binding with invading bacterial and use membrane-bound Dscam as a receptor. However, the mechanisms of secreted Dscam specific binding with bacterial and regulate phagocytosis via membrane-bound receptor still remains largely unknown. This project will find Dscam binding target molecular in bacterial, bacterial binding key amino acid regions in Dscam, the phagocytic signaling pathway that membrane-bound Dscam regulated, and the other phagocytic receptor that binding with secreted Dscam. This project will uncover the mechanism of alternative spliced Dscam specific regulated phagocytosis in Chinese mitten crab, provide an important scientific basis for antibacterial mechanisms in this crab and other crustaceans.