ArticleAmerican journal of physiology. Lung cellular and molecular physiology2017
The CFTR trafficking mutation F508del inhibits the constitutive activity of SLC26A9.
Article in American journal of physiology. Lung cellular and molecular physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- From transporter to motor: Evolutionary and structural insights into the emergence of prestin's area-motor activity in mammals.Protein science : a publication of the Protein Society · 2026Article
- Lack of SLC26A9-mediated chloride secretion causes mucus plugging and severe respiratory distress in neonatal mice.JCI insight · 2025Article
- Single-cell RNA-sequencing co-expression analysis with CFTR and CF modifier genes in lung tissue.Scientific reports · 2025Article
- Selective amino acid formulation enhances anion secretion and restores function in cystic fibrosis mutations.Frontiers in pharmacology · 2025Article
- Chloride/Multiple Anion Exchanger SLC26A Family: Systemic Roles of SLC26A4 in Various Organs.International journal of molecular sciences · 2024Review
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins.International journal of molecular sciences · 2023Review
- Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange.eLife · 2023Article
- Putting bicarbonate on the spot: pharmacological insights for CFTR correction in the airway epithelium.Frontiers in pharmacology · 2023Article
- Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.International journal of molecular sciences · 2022Article
- Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease.NPJ genomic medicine · 2022Article
- Expression of SLC26A9 in Airways and Its Potential Role in Asthma.International journal of molecular sciences · 2022Article
- SLC26A9 as a Potential Modifier and Therapeutic Target in Cystic Fibrosis Lung Disease.Biomolecules · 2022Review
- SLC26A9 is selected for endoplasmic reticulum associated degradation (ERAD) via Hsp70-dependent targeting of the soluble STAS domain.The Biochemical journal · 2021Article
- Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9.International journal of molecular sciences · 2021Article
- Separating the contributions of SLC26A9 and CFTR to anion secretion in primary human bronchial epithelia.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- CyFi-MAP: an interactive pathway-based resource for cystic fibrosis.Scientific reports · 2021Article
- SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2021Observational
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8 authors at 2 institutions in 1 country.
Funding
Abstract
Several members of the SLC26A family of anion transporters associate with CFTR, forming complexes in which CFTR and SLC26A functions are reciprocally regulated. These associations are thought to be facilitated by PDZ scaffolding interactions. CFTR has been shown to be positively regulated by NHERF-1, and negatively regulated by CAL in airway epithelia. However, it is unclear which PDZ-domain protein(s) interact with SLC26A9, a SLC26A family member found in airway epithelia. We have previously shown that primary, human bronchial epithelia (HBE) from non-CF donors exhibit constitutive anion secretion attributable to SLC26A9. However, constitutive anion secretion is absent in HBE from CF donors. We examined whether changes in SLC26A9 constitutive activity could be attributed to a loss of CFTR trafficking, and what role PDZ interactions played. HEK293 coexpressing SLC26A9 with the trafficking mutant F508del CFTR exhibited a significant reduction in constitutive current compared with cells coexpressing SLC26A9 and wt CFTR. We found that SLC26A9 exhibits complex glycosylation when coexpressed with F508del CFTR, but its expression at the plasma membrane is decreased. SLC26A9 interacted with both NHERF-1 and CAL, and its interaction with both significantly increased with coexpression of wt CFTR. However, coexpression with F508del CFTR only increased SLC26A9's interaction with CAL. Mutation of SLC26A9's PDZ motif decreased this association with CAL, and restored its constitutive activity. Correcting aberrant F508del CFTR trafficking in CF HBE with corrector VX-809 also restored SLC26A9 activity. We conclude that when SLC26A9 is coexpressed with F508del CFTR, its trafficking defect leads to a PDZ motif-sensitive intracellular retention of SLC26A9.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.