Terminal glycosylation in cystic fibrosis

• Published in: BBA - Molecular Basis of Disease Vol. 1455; no. 2; pp. 241 - 253
• Main Authors: Scanlin, Thomas F., Glick, Mary Catherine
• Format: Book Review Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 08.10.1999
• Subjects: alpha-L-Fucosidase - genetics; alpha-L-Fucosidase - metabolism; Animals; Carbohydrate Sequence; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis - therapy; Cystic Fibrosis Transmembrane Conductance Regulator - chemistry; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Cystic fibrosis transmembrane regulator; Epithelial Cells - metabolism; Fibroblasts - metabolism; Genetic Therapy; Glycosylation; Glycosylation in cystic fibrosis; Humans; Lung - metabolism; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Mutation; Oligosaccharides - metabolism; Spectrometry, Mass, Fast Atom Bombardment; Terminal glycosylation; Glycosylation in cystic fibrosis; Cystic fibrosis transmembrane regulator; Cystic fibrosis; Terminal glycosylation
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/S0925-4439(99)00059-9

Cystic fibrosis (CF) is a common genetic disease for which the gene was identified within the last decade. Pulmonary disease predominates in this ultimately fatal disease and current therapy only slows the progression. CF transmembrane regulator (CFTR), the gene product, is an integral membrane glycoprotein that normally functions as a chloride channel in epithelial cells. The most common mutation, ΔF508, results in mislocalization and altered glycosylation of CFTR. Altered fucosylation and sialylation are hallmarks of both membrane and secreted glycoproteins in CF and the focus here is on these investigations. Oligosaccharides from CF membrane glycoproteins have the Lewis x, selectin ligand in terminal positions. In addition, two major bacterial pathogens in CF, Pseudomonas aeruginosa and Haemophilus influenzae, have binding proteins, which recognize fucose in α1,3 linkage and asialoglycoconjugates. We speculate that the altered terminal glycosylation of airway epithelial glycoproteins in CF contributes to the chronic infection and robust inflammatory response in the CF lung. Understanding the effects of mutant CFTR on glycosylation may provide further insight into the regulation of glycoconjugate processing as well as therapy for CF.