Dysfunction of CFTR Bearing the Delta F508 Mutation

J Cell Sci Suppl. 1993;17:235-9.

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in patients with cystic fibrosis (CF). The most common CF-associated mutation is deletion of phenylalanine at residue 508, CFTR delta F508. When expressed in heterologous cells, CFTR bearing the delta F508 mutation fails to progress through the normal biosynthetic pathway and fails to traffic to the plasma membrane. As a result, CFTR delta F508 is mislocalized and is not present in the apical membrane of primary cultures of airway epithelia. Consequently, the apical membrane of CF airway epithelia is Cl- -impermeable, a defect that probably contributes to the pathogenesis of the disease.

Publication types

  • Review

MeSH terms

  • Cell Membrane / metabolism
  • Chloride Channels / genetics
  • Chloride Channels / metabolism
  • Cystic Fibrosis / etiology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelium / metabolism
  • Glycosylation
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Molecular Structure
  • Protein Processing, Post-Translational
  • Respiratory System / metabolism
  • Sequence Deletion
  • Temperature

Substances

  • CFTR protein, human
  • Chloride Channels
  • Membrane Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator