CFTR Function and Prospects for Therapy
Abstract
Mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) epithelial anion channel cause cystic fibrosis (CF). The multidomain integral membrane glycoprotein, a member of the adenine nucleotide-binding cassette (ABC) transporter family, conserved in metazoan salt-transporting tissues, is required to control ion and fluid homeostasis on epithelial surfaces. This review considers different therapeutic strategies that have arisen from knowledge of CFTR structure and function as well as its biosynthetic processing, intracellular trafficking, and turnover.
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F508del leads to severely impaired processing, plasma membrane expression, and stability, as well as defective gating of F508del-CFTR.
“This leads to a combination of defects, consisting of severely impaired processing, plasma membrane (PM) expression, and stability, as well as defective gating of the F508del-CFTR (12–14).”
From Allosteric folding correction of F508del and rare CFTR mutants by elexacaftor-tezacaftor-ivacaftor (Trikafta) combination (2020) · cites this paper as [14]
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- Authors
- Riordan, J. R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Riordan, John R.
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2008-06-01
- Volume
- 77
- Issue
- 1
- Pages
- 701-726
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2108047993
- Cited by
- 610
- References
- 0
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 12 · 2023: 20 · 2022: 20 · 2021: 30 · 2020: 36 · 2019: 26 · 2018: 33 · 2017: 31 · 2016: 39 · 2015: 45 · 2014: 47 · 2013: 44 · 2012: 48
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- CFTR, cystic fibrosis, CFTR mutations, CFTR function, intracellular trafficking, CFTR-targeted therapy
- MeSH terms
- Animals, Anions, Cystic Fibrosis, Endocytosis, Endoplasmic Reticulum, Humans, Models, Biological, Molecular Conformation, Mutation, Protein Denaturation, Salts, Genetic Therapy, Protein Folding, Cystic Fibrosis Transmembrane Conductance Regulator, Cryoelectron Microscopy
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