脂筏相关蛋白β-adducin调控PSGL-1介导的中性粒细胞起始黏附的作用和机制研究

项目名称： 脂筏相关蛋白β-adducin调控PSGL-1介导的中性粒细胞起始黏附的作用和机制研究

项目编号： No.31471332

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 王晓光

作者单位： 长春师范大学

项目金额： 70万元

中文摘要： 中性粒细胞是参与炎症反应的重要免疫细胞之一。中性粒细胞向炎症部位募集是由一系列黏附分子介导的，其中组成性表达于中性粒细胞表面的PSGL-1在细胞的起始黏附过程中发挥重要作用。我们最近的研究发现细胞膜上的脂筏结构对于PSGL-1介导的中性粒细胞黏附至关重要，同时我们在中性粒细胞的脂筏结构中鉴定到一种新的脂筏相关蛋白β-adducin。初步的分析表明，β-adducin可能在调节脂筏结构及中性粒细胞起始黏附中具有重要作用。本研究将在前期工作的基础上深入探讨①β-adducin对PSGL-1和脂筏簇集以及中性粒细胞起始黏附的调控作用；②确定与β-adducin相互作用，并调控其活性的靶蛋白；③揭示靶蛋白与β-adducin相互作用并影响PSGL-1和脂筏簇集及中性粒细胞向炎症部位募集的分子机制。本研究内容的阐明对于深入了解中性粒细胞的生理功能和在炎症部位募集的分子机制具有重要意义。

中文关键词： 中性粒细胞；起始黏附；脂筏结构；PSGL-1；β-adducin

英文摘要： Neutrophil is one of the most important immune cells. The recruitment of neutrophil to a site of inflammation is mediated by a series of adhesion molecules. Among them, PSGL-1 which is constitutively expressed on microvilli of almost all kind of leukocytes plays a critical role in neutrophil adhesion. Our recent work reported that lipid raft, a liquid ordered plasma membrane microdomain, is necessary for PSGL-1 mediated initial adhesion of neutrophils, and we identified a new lipid raft associated protein, β-adducin. Based on the results of some experiments and the previous reported data, we speculate that β-adducin play a critical role in regulating lipid raft structure and neutrophil initial adhesion. In this study we will ①explore the role of β-adducin in regulating coalescences of PSGL-1 and lipid raft as well as the initial adhesion of neutrophil; ②identify the target proteins that interact with β-adducin and regulate its activity; ③bring to light the mechanism that β-adducin interact with the target proteins and regulate the coalescences of PSGL-1 and lipid raft and neutrophil recruitment in inflammation sites. The results will greatly help us to understand the molecular mechanism of neutrophil recruitment and will benefit the drug development targeting neutrophil adhesion.

英文关键词： neutrophils;initial adhesion;lipid raft structure;PSGL-1;β-adducin