Aberrant CFTR-dependent HCO3 - transport in mutations associated with cystic fibrosis

Joo Young Choi, Daniella Muallem, Kirill Kiselyov, Min Goo Lee, Philip J. Thomas, Shmuel Muallem

Research output: Contribution to journalArticle

290 Citations (Scopus)

Abstract

Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Initially, Cl- conductance in the sweat duct was discovered to be impaired in CF1, a finding that has been extended to all CFTR-expressing cells. Subsequent cloning of the gene showed that CFTR functions as a cyclic-AMP-regulated Cl- channel and some CF-causing mutations inhibit CFTR Cl- channel activity. The identification of additional CF-causing mutants with normal Cl- channel activity indicates, however, that other CFTR-dependent processes contribute to the disease. Indeed, CFTR regulates other transporters, including Cl--coupled HCO3 - transport. Alkaline fluids are secreted by normal tissues, whereas acidic fluids are secreted by mutant CFTR-expressing tissues, indicating the importance of this activity. HCO3 - and pH affect mucin viscosity and bacterial binding. We have examined Cl--coupled HCO3 - transport by CFTR mutants that retain substantial or normal Cl- channel activity. Here we show that mutants reported to be associated with CF with pancreatic insufficiency do not support HCO3 - transport, and those associated with pancreatic sufficiency show reduced HCO3 - transport. Our findings demonstrate the importance of HCO3 - transport in the function of secretory epithelia and in CF.

Original languageEnglish (US)
Pages (from-to)94-97
Number of pages4
JournalNature
Volume410
Issue number6824
DOIs
StatePublished - Mar 1 2001

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Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Mutation
Exocrine Pancreatic Insufficiency
Sweat
Mucins
Viscosity
Cyclic AMP
Organism Cloning
Epithelium

ASJC Scopus subject areas

  • General

Cite this

Choi, J. Y., Muallem, D., Kiselyov, K., Lee, M. G., Thomas, P. J., & Muallem, S. (2001). Aberrant CFTR-dependent HCO3 - transport in mutations associated with cystic fibrosis. Nature, 410(6824), 94-97. https://doi.org/10.1038/35065099

Aberrant CFTR-dependent HCO3 - transport in mutations associated with cystic fibrosis. / Choi, Joo Young; Muallem, Daniella; Kiselyov, Kirill; Lee, Min Goo; Thomas, Philip J.; Muallem, Shmuel.

In: Nature, Vol. 410, No. 6824, 01.03.2001, p. 94-97.

Research output: Contribution to journalArticle

Choi, JY, Muallem, D, Kiselyov, K, Lee, MG, Thomas, PJ & Muallem, S 2001, 'Aberrant CFTR-dependent HCO3 - transport in mutations associated with cystic fibrosis', Nature, vol. 410, no. 6824, pp. 94-97. https://doi.org/10.1038/35065099
Choi, Joo Young ; Muallem, Daniella ; Kiselyov, Kirill ; Lee, Min Goo ; Thomas, Philip J. ; Muallem, Shmuel. / Aberrant CFTR-dependent HCO3 - transport in mutations associated with cystic fibrosis. In: Nature. 2001 ; Vol. 410, No. 6824. pp. 94-97.
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