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In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
10:05

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Purinergic signaling underlies CFTR control of human airway epithelial cell volume

Gavin M Braunstein1, Akos Zsembery, Torry A Tucker

  • 1Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
|October 7, 2004
PubMed
Abstract

Insights

Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function impairs airway epithelial cell volume regulation. This defect in cystic fibrosis (CF) is linked to dysregulated ion and water transport, impacting CFTR-driven signaling pathways.

Area of Science:

  • Cell Biology
  • Physiology
  • Ion Transport

Background:

  • Cystic fibrosis (CF) is characterized by loss of cystic fibrosis transmembrane conductance regulator (CFTR) function.
  • CFTR dysfunction leads to dysregulation of ion channels, water channels, and acid-base transporters in epithelia.
  • This study investigates the hypothesis that these dysregulations cause defects in human airway epithelial cell volume regulation.

Purpose of the Study:

  • To assess cell volume regulation in human airway epithelial cells with and without functional CFTR.
  • To investigate the role of CFTR in regulating cell volume and associated signaling pathways.
  • To determine if CFTR dysfunction contributes to defective ion and water transport in CF.

Main Methods:

  • Real-time assessment of cell volume and regulatory volume decrease (RVD) using electronic cell sizing (Coulter Counter Multisizer III).
  • Evaluation in non-CF, CF, and CFTR-complemented CF human airway epithelial cells.
  • Validation of cell volume assays using SPQ halide fluorescence assay for hypotonicity-induced chloride efflux.

Main Results:

  • Cystic fibrosis transmembrane conductance regulator (CFTR) governs human airway epithelial cell volume regulation via autocrine ATP signaling.
  • Normal regulatory volume decrease (RVD) was observed in non-CF and wild-type (WT)-CFTR-transfected CF cells.
  • CF cells expressing CFTR mutants (DeltaF508, G551D, S1455X) failed to RVD, but this was rescued by purinergic receptor agonists.

Conclusions:

  • Loss of CFTR function and CFTR-driven autocrine ATP signaling contribute to defective cell volume regulation in CF airway epithelia.
  • Dysregulated ion, water, and acid-base transport in CF are linked to impaired CFTR function.
  • Targeting purinergic signaling pathways may offer therapeutic potential for CF-related epithelial defects.

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