CFTR chloride channel regulation by an interdomain interaction

Academic Article

Abstract

  • The cystic fibrosis gene encodes a chloride channel CFTR (cystic fibrosis transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates CFTR by an unknown mechanism. The amino-terminal cytoplasmic tail of CFTR was found to control protein kinase A-dependent channel gating through a physical interaction with the R domain. This regulatory activity mapped to a cluster of acidic residues in the NH2-terminal tail; mutating these residues proportionately inhibited R domain binding and CFTR channel function. CFTR activity appears to be governed by an interdomain interaction involving the amino-terminal tail which is a potential target for physiologic and pharmacologic modulators of this ion channel.
  • Authors

    Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Naren AP; Cormet-Boyaka E; Fu J; Villain M; Blalock JE; Quick MW; Kirk KL
  • Start Page

  • 544
  • End Page

  • 548
  • Volume

  • 286
  • Issue

  • 5439