Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia

Lynda S Ostedgaard; Christoph Randak; Tatiana Rokhlina; Philip Karp; Daniel Vermeer; Katherine J Ashbourne Excoffon; Michael J Welsh

doi:10.1073/pnas.2627982100

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Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia

Journal article

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Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia

Lynda S Ostedgaard, Christoph Randak, Tatiana Rokhlina, Philip Karp, Daniel Vermeer, Katherine J Ashbourne Excoffon and Michael J Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.100(4), pp.1937-1942

02/18/2003

DOI: 10.1073/pnas.2627982100

PMCID: PMC149937

PMID: 12578973

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Abstract

To better understand the function of the conserved C terminus of the cystic fibrosis (CF) transmembrane conductance regulator, we studied constructs containing deletions in the C-terminal tail. When expressed in well differentiated CF airway epithelia, each construct localized predominantly to the apical membrane and generated transepithelial Cl − current. The results suggested that neither the C-terminal P SD-95/ D iscs-large/ Z O-1 (PDZ)-interacting motif nor other C-terminal sequences were absolutely required for apical expression in airway epithelia. Surprisingly, deleting an acidic cluster near the C terminus reduced both channel opening rate and transepithelial Cl − transport, indicating that it influences channel gating. These results may help explain the relative paucity of CF-associated mutations in the C terminus.

Biological Sciences

Details

Title: Subtitle: Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia
Creators: Lynda S Ostedgaard - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Christoph Randak - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Tatiana Rokhlina - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Philip Karp - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Daniel Vermeer - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Katherine J Ashbourne Excoffon - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Michael J Welsh - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.100(4), pp.1937-1942
DOI: 10.1073/pnas.2627982100
PMID: 12578973
PMCID: PMC149937
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 02/18/2003
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Stead Family Department of Pediatrics; Neurosurgery; Internal Medicine
Record Identifier: 9984014018702771

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