Journal
EMBO JOURNAL
Volume 21, Issue 21, Pages 5662-5672Publisher
WILEY
DOI: 10.1093/emboj/cdf580
Keywords
CFTR; cystic fibrosis; electrogenic Cl-; HCO3- transporters; SLC26
Categories
Funding
- NIDCR NIH HHS [DE12309, R01 DE012309] Funding Source: Medline
- NIDDK NIH HHS [DK49835, R01 DK038938, R01 DK049835, DK38938, R37 DK049835] Funding Source: Medline
Ask authors/readers for more resources
Aberrant HCO3- transport is a hallmark of cystic fibrosis (CF) and is associated with aberrant Cl--dependent HCO3- transport by the cystic fibrosis transmembrane conductance regulator (CFTR). We show here that HCO3- current by CFTR cannot account for CFTR-activated HCO3- transport and that CFTR does not activate AE1-AE4. In contrast, CFTR markedly activates Cl- and OH-/HCO3- transport by members of the SLC26 family DRA, SLC26A6 and pendrin. Most notably, the SLC26s are electrogenic transporters with isoform-specific stoichiometries. DRA activity occurred at a Cl-/HCO3- ratio greater than or equal to2. SLC26A6 activity is voltage regulated and occurred at HCO3-/Cl- greater than or equal to2. The physiological significance of these findings is demonstrated by interaction of CFTR and DRA in the mouse pancreas and an altered activation of DRA by the R117H and G551D mutants of CFTR. These findings provide a molecular mechanism for epithelial HCO3- transport (one SLC26 transporter-electrogenic transport; two SLC26 transporters with opposite stoichiometry in the same membrane domain-electroneutral transport), the CF-associated aberrant HCO3- transport, and reveal a new function of CFTR with clinical implications for CF and congenital chloride diarrhea.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available