ANO5:新的钙激活的氯离子通道的功能

项目名称： ANO5:新的钙激活的氯离子通道的功能

项目编号： No.31200858

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生理学与整合生物学

项目作者： 田岳民

作者单位： 新乡医学院

项目金额： 24万元

中文摘要： ANO1和 ANO2 最近被报道是钙激活的氯离子通道的分子基础，作为同一家族的ANO5,又名TMEM16E，GDD1，LGMD2L,主要分布于骨骼肌细胞以及成骨细胞和软骨细胞中。它的基因突变表现为骨骼肌病以及骨骼的矿物质化和变脆。在肌细胞内ANO5主要分布于胞内囊泡，在细胞膜也有表达。ANO5基因突变的病人表现为肌细胞膜损伤修复缺陷。经我们前期工作首次证明ANO5也是钙激活的氯离子通道，而且它只有在超生理条件的高钙作用下才可以被激活。我们认为ANO5很有可能通过胞吐作用，从胞内囊泡转移到细胞膜，进一步参与细胞膜的修复。本课题拟采用分子生物学技术，荧光显微镜技术观察ANO5在细胞内的表达定位和应对细胞膜损伤的反应，膜片钳技术结合基因过表达等方法研究ANO5对于细胞膜损伤修复的作用。

中文关键词： Ano5；消化道；骨骼肌；损伤；修复

英文摘要： The molecular role of Ca2+ activated Cl- channel(CACC) has been found recently as ANO(Anoctamin)1 and ANO2. As one of the member of the same family, ANO5， also named as TMEM16E, GDD1, LGMD2L mainly expressed in skeleten musal cells, has been first found by us as CACC too. It is reported that ANO5 mutations in patients, chondrocytes and osteoblasts.Mutations in ANO5 result in a spectrum of musculoskeletal disorders and abnormal bone mineralization and bone fragility.ANO5 resides predominantly in intracellular membrane vesicles and also in plasma membrane.ANO5 mutant patient show defective skeletal muscle membrane repair. According to our results ANO5 is also a Ca2+ activated Cl- channel, and it can only be activated under a unphysiology high Ca2+ condition. The hypothesis is ANO5 located in the endoplasmic vesicals can repair plasma membrane wound through exocytosis. We plan to use molecular biology technique and electromicroscope to know the expression and localization and traffic of ANO5 in the cell, and use patch lamp and Ussing chamber recording to detect over expressed of ANO5 to know the function in cell membrane wound repairing.

英文关键词： Ano5；Digestive tract；Skeletal muscle；Damage；Repair