Is the ENaC Dysregulation in CF an Effect of Protein-Lipid Interaction in the Membranes?

Int J Mol Sci. 2021 Mar 8;22(5):2739. doi: 10.3390/ijms22052739.

Abstract

While approximately 2000 mutations have been discovered in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), only a small amount (about 10%) is associated with clinical cystic fibrosis (CF) disease. The discovery of the association between CFTR and the hyperactive epithelial sodium channel (ENaC) has raised the question of the influence of ENaC on the clinical CF phenotype. ENaC disturbance contributes to the pathological secretion, and overexpression of one ENaC subunit, the β-unit, can give a CF-like phenotype in mice with normal acting CFTR. The development of ENaC channel modulators is now in progress. Both CFTR and ENaC are located in the cell membrane and are influenced by its lipid configuration. Recent studies have emphasized the importance of the interaction of lipids and these proteins in the membranes. Linoleic acid deficiency is the most prevailing lipid abnormality in CF, and linoleic acid is an important constituent of membranes. The influence on sodium excretion by linoleic acid supplementation indicates that lipid-protein interaction is of importance for the clinical pathophysiology in CF. Further studies of this association can imply a simple clinical adjuvant in CF therapy.

Keywords: CFTR; linoleic acid; renal excretion; sodium; supplementation; sweat.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • Cell Membrane / pathology
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism*
  • Humans
  • Linoleic Acid / deficiency*
  • Linoleic Acid / metabolism
  • Mice

Substances

  • CFTR protein, human
  • Epithelial Sodium Channels
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Linoleic Acid