Regulatory Interaction between CFTR and the SLC26 Transporters

Nikolay Shcheynikov, Shigeru B.H. Ko, Weizhong Zeng, Joo Young Choi, Michael R. Dorwart, Philip J. Thomas, Shmuel Muallem

Research output: Chapter in Book/Report/Conference proceedingChapter


Most epithelia that express CFTR secrete fluid rich in HCO3- and poor in Cl- that is generated by a CFTR-dependent Cl- absorption and HCO3- secretion process that when aberrant leads to human diseases such as cystic fibrosis and congenital chloride diarrhoea. Epithelial Cl- absorption and HCO3- secretion require expression of CFTR and other Cl- and HCO3- transporters in the luminal membrane of the secreting cells. Recent advances in understanding this critical epithelial function revealed that the luminal Cl- and HCO3- transporters are members of the SLC26 family. Characterization of several members of the family reveals that all characterized thus far are electrogenic with an isoform specific Cl-/HCO3- transport stoichiometry. In vivo these transporters exist in a transporting complex with CFTR. The SLC26 transporters and CFTR are recruited to the complex by binding to scaffolds containing PDZ domains. Upon stimulation and PKA-dependent phosphorylation of CFTR R domain, the R domain binds to the SLC26 transporter STAS domain. Interaction of the R and STAS domains results in a marked and mutual activation of CFTR and the SLC26 transporters. The significance of this mode of regulation to epithelial Cl- absorption and HCO3- secretion is obvious.

Original languageEnglish
Title of host publicationEpithelial Anion Transport in Health and Disease
Subtitle of host publicationThe Role of the SLC26 Transporters Family
PublisherWiley Blackwell
Number of pages10
ISBN (Electronic)9780470029572
ISBN (Print)0470016248, 9780470016244
Publication statusPublished - 2008 Oct 7
Externally publishedYes


  • CFTR
  • Cl- absorption
  • Electrogenic
  • Epithelial
  • HCO3- secretion
  • Interaction
  • Mutual activation
  • R-STAS domain
  • SLC26 transporters
  • SLC26A3
  • SLC26A6

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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