AE2 CI/HCO3 Exchanger and Transepithelial Ion Transport

描述（由申请人提供）：本研究的总体目标是确定AE2阴离子交换剂在结肠和胆道系统上皮细胞中的生理作用。AE2的功能是在许多细胞类型的细胞膜上用一个氯离子交换一个碳酸氢盐离子。这种活性导致氯离子净运动进入细胞（在那里它可以被其他转运体分泌）和碳酸氢盐净运动出细胞。在结肠中，有人提出AE2介导氯离子进入上皮细胞以支持经上皮分泌，并在碳酸氢盐吸收过程中为细胞中的碳酸氢盐提供退出途径。在胆道系统中，AE2被认为在胆尖膜上表达，并介导碳酸氢盐分泌到胆汁中的电沉默成分。利用基因靶向技术，本研究的目的是1)验证AE2在结肠和胆道上皮细胞中对氯化物和碳酸氢盐运输至关重要的假设，2)开发肠道特异性的AE2基因敲除来评估AE2在结肠碳酸氢盐吸收中的作用。

DESCRIPTION (provided by applicant): The overall goal of this research is to determine the physiological role of the AE2 anion exchanger in epithelial cells that line the colon and biliary system. AE2 functions to exchange one chloride for one bicarbonate ion across the membrane of many cell types. This activity results in net chloride movement into the cell (where it is available for secretion by other transporters) and net bicarbonate movement out of the cell. In the colon, AE2 has been proposed to mediate chloride uptake into the epithelial cells to support transepithelial secretion and to provide an exit pathway for bicarbonate from the cell during bicarbonate absorption. In the biliary system, AE2 is believed to be expressed on the apical membrane and mediate the electrically-silent component of bicarbonate secretion into bile. Using gene-targeting technology, the aims of this proposal are i) to test the hypotheses that AE2 is critical to chloride and bicarbonate transport in colonic and biliary epithelial cells and 2) develop an intestine-specific AE2 knockout to evaluate the role of AE2 in colonic bicarbonate absorption.