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

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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Poschet, J. F. Boucher, J. C. Tatterson, L. Skidmore, J. Van Dyke, R. W. Deretic, V.
Description	Author Affiliation: Poschet JF ( Department of Microbiology and Immunology University of Michigan Medical School, Ann Arbor, MI 48109, USA.);
Abstract	The CFTR gene encodes a transmembrane conductance regulator, which is dysfunctional in patients with cystic fibrosis (CF). The mechanism by which defective CFTR (CF transmembrane conductance regulator) leads to undersialylation of plasma membrane glycoconjugates, which in turn promote lung pathology and colonization with Pseudomonas aeruginosa causing lethal bacterial infections in CF, is not known. Here we show by ratiometric imaging with lumenally exposed pH-sensitive green fluorescent protein that dysfunctional CFTR leads to hyperacidification of the trans-Golgi network (TGN) in CF lung epithelial cells. The hyperacidification of TGN, glycosylation defect of plasma membrane glycoconjugates, and increased P. aeruginosa adherence were corrected by incubating CF respiratory epithelial cells with weak bases. Studies with pharmacological agents indicated a role for sodium conductance, modulated by CFTR regulatory function, in determining the pH of TGN. These studies demonstrate the molecular basis for defective glycosylation of lung epithelial cells and bacterial pathogenesis in CF, and suggest a cure by normalizing the pH of intracellular compartments.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cystic Fibrosis Transmembrane Conductance Regulator Metabolism Cystic Fibrosis Glycoproteins Lung Membrane Proteins Pseudomonas Aeruginosa Acids Bacterial Adhesion Cell Line Glycosylation Green Fluorescent Proteins Luminescent Proteins Membrane Glycoproteins Proton-Translocating ATPases Antagonists & Inhibitors Physiology Recombinant Fusion Proteins Sialyltransferases Sodium-Potassium-Exchanging ATPase Trans-Golgi Network Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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