AE2 CI/HCO3 Exchanger and Transepithelial Ion Transport

描述(由申请人提供)：这项研究的总体目标是确定AE2阴离子交换器在结肠和胆道系统中的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种氯化物交换一种碳酸氢根离子。这种活动导致净氯化物进入细胞(在那里它可供其他转运体分泌)和净碳酸氢盐离开细胞。在结肠中，AE2被认为介导氯摄取进入上皮细胞，以支持跨上皮分泌，并在碳酸氢盐吸收过程中为碳酸氢盐从细胞中退出提供一条途径。在胆道系统中，AE2被认为表达在顶膜上，并介导碳酸氢盐分泌到胆汁中的电子沉默成分。利用基因打靶技术，这项建议的目的是：1)测试AE2对结肠和胆管上皮细胞中氯和碳酸氢盐转运至关重要的假说；2)建立肠道特异的AE2基因敲除方法，以评估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.