ArticleThe Journal of biological chemistry2012
Keratin K18 increases cystic fibrosis transmembrane conductance regulator (CFTR) surface expression by binding to its C-terminal hydrophobic patch.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- The Adhesion G-Protein-Coupled Receptor GPR115/Cells · 2022Article
- Keratin 8 is a scaffolding and regulatory protein of ERAD complexes.Cellular and molecular life sciences : CMLS · 2022Article
- CFTR is a negative regulator of γδ T cell IFN-γ production and antitumor immunity.Cellular & molecular immunology · 2021Article
- Identification of a Novel Link between the Intermediate Filament Organizer IFO-1 and Cholesterol Metabolism in theInternational journal of molecular sciences · 2020Article
- [Interaction between PSF and cytokeratin 18 mediates PSF relocation to cell membrane and maintains chemosensitivity of myeloid leukemia].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2020Article
- CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathway degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Structural mechanisms for defective CFTR gating caused by the Q1412X mutation, a severe Class VI pathogenic mutation in cystic fibrosis.The Journal of physiology · 2019Article
- Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-MediatedFrontiers in cellular and infection microbiology · 2018Article
- New insights into interactions between the nucleotide-binding domain of CFTR and keratin 8.Protein science : a publication of the Protein Society · 2017Article
- Intermediate Filaments and the Plasma Membrane.Cold Spring Harbor perspectives in biology · 2017Review
- Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.Frontiers in pharmacology · 2017Review
- Review
- Keratin 8 knockdown leads to loss of the chloride transporter DRA in the colon.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Exploring Mouse Protein Function via Multiple Approaches.PloS one · 2016Article
- Article
- Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain.EMBO molecular medicine · 2013Article
- Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels.The Journal of biological chemistryArticle
- Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity.Tissue barriersReview
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCFTR function is tightly regulated by many interacting proteins.
resultsIntermediate filament protein keratin 18 increases the cell surface expression of CFTR by interacting with the C-terminal hydrophobic patch of CFTR.
conclusionK18 controls the function of CFTR. SIGNIFICANCE: These findings offer novel insights into the regulation of CFTR and suggest that K18 and its dimerization partner, K8, may be modifier genes in cystic fibrosis. Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to cystic fibrosis, but the regulation of CFTR is not fully understood. Here, we identified the intermediate filament protein keratin K18 (K18) as a CFTR-binding protein by various approaches. We mapped a highly conserved "hydrophobic patch" ((1413)FLVI(1416)) in the CFTR C-terminus, known to determine plasmalemmal CFTR stability, as the K18-binding site. On the other hand, the C-terminal tail of K18 was found to be a critical determinant for binding CFTR. Overexpression of K18 in cells robustly increased the surface expression of wild-type CFTR, whereas depletion of K18 through RNA interference specifically diminished it. K18 binding increased the surface expression of CFTR by accelerating its apical recycling rate without altering CFTR biosynthesis, maturation, or internalization. Importantly, CFTR surface expression was markedly reduced in duodenal and gallbladder epithelia of K18(-/-) mice. Taken together, our results suggest that K18 increases the cell surface expression of CFTR by interacting with the CFTR C-terminal hydrophobic patch. These findings offer novel insights into the regulation of CFTR and suggest that K18 and its dimerization partner, K8, may be modifier genes in cystic fibrosis.
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