Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung

摘要: The CFTR gene encodes a transmembrane conductance regulator, which is dysfunctional in patients with cystic fibrosis (CF). mechanism by defective (CF regulator) leads to undersialylation of plasma membrane glycoconjugates, turn promote lung pathology and colonization Pseudomonas aeruginosa causing lethal bacterial infections CF, not known. Here we show ratiometric imaging lumenally exposed pH-sensitive green fluorescent protein that hyperacidification the trans-Golgi network (TGN) CF epithelial cells. TGN, glycosylation defect increased P. adherence were corrected incubating respiratory cells weak bases. Studies pharmacological agents indicated role for sodium conductance, modulated regulatory function, determining pH TGN. These studies demonstrate molecular basis pathogenesis suggest cure normalizing intracellular compartments.