人内源性多肽与T细胞钾通道Kv1.3相互作用的发现及功能机制研究

项目名称： 人内源性多肽与T细胞钾通道Kv1.3相互作用的发现及功能机制研究

项目编号： No.31470812

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： 吴英亮

作者单位： 武汉大学

项目金额： 90万元

中文摘要： 约100种人源钾通道分布广泛并发挥重要生理病理功能，如T细胞钾通道Kv1.3与自身免疫疾病密切相关并成为新药研发靶标。不同人源钾通道（作为盾）的电流广泛地被有毒动物（如蝎、蛇等）毒液中毒素多肽（作为矛）所抑制，但在人和其它哺乳动物体内是否存在抑制钾通道电流的内源性多肽仍是一个未解之谜。基于课题组在动物毒素多肽与钾通道相互作用的系统工作积累，本项目围绕人内源性多肽与T细胞钾通道Kv1.3的相互作用及功能机制关键科学问题，拟创新开展：筛选与鉴定人内源性多肽与T细胞钾通道Kv1.3的相互作用；研究内源性多肽与钾通道Kv1.3相互作用对T细胞的细胞因子分泌影响；揭示内源性多肽与钾通道Kv1.3作用的分子机制。这些工作将揭示人体内源性多肽（矛）与钾通道（盾）相互依存的自然现象，发现内源性多肽作用T细胞产生新的免疫调节功能与机制，开辟作用钾通道内源性多肽的发现及其功能机制研究的新领域。

中文关键词： T细胞；钾离子通道Kv1.3；内源性多肽；相互作用；功能机制

英文摘要： In human body, about 100 ubiquitous potassium channels play important roles in the physiological and pathological activities. For example, the potassium channel Kv1.3 in T cells is closely related to the autoimmune diseases and has been the target of new drugs. Different human potassium channels (as a kind of shield) are widely inhibited by peptide toxins (as a kind of spear) from venomous animals, such as scorpions and snakes. However, whether there is an endogenous peptide inhibitor of potassium channels in an individual human or other mammalian remains a question so far. Based on the our systematic work of toxin peptide-potassium channel interactions, this project will focus on the key scientific question of interactions between human endogenous peptides and potassium channel Kv1.3 in T cells and their binding mechanisms, and carry out following work: Screening and identifying interactions between human endogenous peptides and potassium channel Kv1.3 in T cells; Investigating the effects of human endogenous peptide-Kv1.3 channel interactions on cytokine secretion in T cells; Revealing the molecular mechnism of endogenous peptide-potassium channel Kv1.3 interactions. All these studies will reveal the natural phenomenon of interdependent relationship between endogenous peptides (as a kind of spear) and potassium channels (as a kind of shield)in the human body, find the novel immune modulation functions of endogenous peptides acting on potassium channel Kv1.3 in T cells, and open a new field of discovery of endogenous peptides acting on potassium channels and their research and application.

英文关键词： T cells;Potassium channel Kv1.3;endogenous peptide;Interactions;function and mechanism