Regulatory interaction between CFTR and the SLC26 transporters

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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

45 Citations (Scopus)

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 HCO 3 - 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 HCO 3 - 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-/HCO 3 - 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 publicationNovartis Foundation Symposium
Pages177-186
Number of pages10
Volume273
Publication statusPublished - 2006
Externally publishedYes

Publication series

NameNovartis Foundation Symposium
Volume273
ISSN (Print)15282511

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PDZ Domains
Secretory Pathway
Cystic Fibrosis
Protein Isoforms
Epithelium
Phosphorylation
Cell Membrane
Congenital chloride diarrhea

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shcheynikov, N., Ko, S., Zeng, W., Joo, Y. C., Dorwart, M. R., Thomas, P. J., & Muallem, S. (2006). Regulatory interaction between CFTR and the SLC26 transporters. In Novartis Foundation Symposium (Vol. 273, pp. 177-186). (Novartis Foundation Symposium; Vol. 273).

Regulatory interaction between CFTR and the SLC26 transporters. / Shcheynikov, Nikolay; Ko, Shigeru; Zeng, Weizhong; Joo, Young Choi; Dorwart, Michael R.; Thomas, Philip J.; Muallem, Shmuel.

Novartis Foundation Symposium. Vol. 273 2006. p. 177-186 (Novartis Foundation Symposium; Vol. 273).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Shcheynikov, N, Ko, S, Zeng, W, Joo, YC, Dorwart, MR, Thomas, PJ & Muallem, S 2006, Regulatory interaction between CFTR and the SLC26 transporters. in Novartis Foundation Symposium. vol. 273, Novartis Foundation Symposium, vol. 273, pp. 177-186.
Shcheynikov N, Ko S, Zeng W, Joo YC, Dorwart MR, Thomas PJ et al. Regulatory interaction between CFTR and the SLC26 transporters. In Novartis Foundation Symposium. Vol. 273. 2006. p. 177-186. (Novartis Foundation Symposium).
Shcheynikov, Nikolay ; Ko, Shigeru ; Zeng, Weizhong ; Joo, Young Choi ; Dorwart, Michael R. ; Thomas, Philip J. ; Muallem, Shmuel. / Regulatory interaction between CFTR and the SLC26 transporters. Novartis Foundation Symposium. Vol. 273 2006. pp. 177-186 (Novartis Foundation Symposium).
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