Regulatory Interaction between CFTR and the SLC26 Transporters

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

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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: The Role of the SLC26 Transporters Family
PublisherWiley Blackwell
Pages177-186
Number of pages10
ISBN (Print)9780470029572, 0470016248, 9780470016244
DOIs
Publication statusPublished - 2008 Oct 7
Externally publishedYes

Keywords

  • 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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  • Cite this

    Shcheynikov, N., Ko, S., Zeng, W., Choi, J. Y., Dorwart, M. R., Thomas, P. J., & Muallem, S. (2008). Regulatory Interaction between CFTR and the SLC26 Transporters. In Epithelial Anion Transport in Health and Disease: The Role of the SLC26 Transporters Family (pp. 177-186). Wiley Blackwell. https://doi.org/10.1002/0470029579.ch12