cCAMP Regulation of Aquaporin 5

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Aquaporins (AQPs) are water specific membrane channel proteins. AQP5, located in the apical membrane of airway submucosal glands, bronchial epithelium, and type I pneumocytes, likely participates in generation of airway surface secretions. Regulation of AQP5 expression is complex and modulated by a variety of stress conditions, including osmolality and viral infections. AQP5 knockout mice have reduced airway gland secretions and increased bronchoconstriction compared to wild type. Changes in AQP5 expression may alter secretions, and play an important role in the airway physiology. In cultured lung epithelial cells, we observed that short-exposures to cAMP decrease AQP5 protein levels and modify its cellular distribution. Beta-agonists, a mainstay of asthma therapy, stimulate the formation of cAMP, and lead to smooth muscle relaxation, but effect on total airway secretions is not defined. We hypothesize that beta-agonists alter AQP5 expression and subcellular trafficking and can thereby alter airway surface liquid. We will investigate the following aims. Aim#1 : To determine how acute cAMP and beta-agonist stimulation decrease AQP5 expression by investigating mechanisms of protein degradation including changes in ubiquitination. Aim#2: To determine the effects of acute exposure to cAMP and beta-agonist stimulation on AQP5 protein trafficking using immunofluorescence of wild-type and mutant AQP5 constructs.