ArticleThe Journal of biological chemistry2016
VAMP-associated Proteins (VAP) as Receptors That Couple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Proteostasis with Lipid Homeostasis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Photosensitizer proximity labeling captures the lipid and protein interactomes.Nature chemical biology · 2026Article
- Tomato B cell receptor-associated protein 31 homologs enhance thermotolerance by promoting chloroplast PSBW accumulation and stabilizing the PSII-LHCII complex.Plant communications · 2026Article
- Beyond Static Tethering at Membrane Contact Sites: Structural Dynamics and Functional Implications of VAP Proteins.Molecules (Basel, Switzerland) · 2025Review
- Article
- Reduced Sphingosine in Cystic Fibrosis Increases Susceptibility toInternational journal of molecular sciences · 2023Article
- A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome.International journal of molecular sciences · 2023Review
- BAP31 depletion inhibited adipogenesis, repressed lipolysis and promoted lipid droplets abnormal growth via attenuating Perilipin1 proteasomal degradation.International journal of biological sciences · 2023Article
- Caspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD/NFκB-mediated glial inflammation in a Drosophila model of human disease.Human molecular genetics · 2022Article
- Proximity Profiling of the CFTR Interaction Landscape in Response to Orkambi.International journal of molecular sciences · 2022Article
- CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.Molecular systems biology · 2022Article
- Review
- Targeted transcriptome analysis using synthetic long read sequencing uncovers isoform reprograming in the progression of colon cancer.Communications biology · 2021Article
- Proteomics and Metabolomics for Cystic Fibrosis Research.International journal of molecular sciences · 2020Review
- An Innovative Lipidomic Workflow to Investigate the Lipid Profile in a Cystic Fibrosis Cell Line.Cells · 2020Article
- The bidirectional relationship between CFTR and lipids.Communications biology · 2020Review
- Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure.Molecular diagnosis & therapy · 2019Review
- SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in aDisease models & mechanisms · 2019Article
- Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress.International journal of molecular sciences · 2018Article
- Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Emerging Links between Lipid Droplets and Motor Neuron Diseases.Developmental cell · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Unesterified cholesterol accumulates in late endosomes in cells expressing the misfolded cystic fibrosis transmembrane conductance regulator (CFTR). CFTR misfolding in the endoplasmic reticulum (ER) or general activation of ER stress led to dynein-mediated clustering of cholesterol-loaded late endosomes at the Golgi region, a process regulated by ER-localized VAMP-associated proteins (VAPs). We hypothesized that VAPs serve as intracellular receptors that couple lipid homeostasis through interactions with two phenylalanines in an acidic track (FFAT) binding signals (found in lipid sorting and sensing proteins, LSS) with proteostasis regulation. VAPB inhibited the degradation of ΔF508-CFTR. The activity was mapped to the ligand-binding major sperm protein (MSP) domain, which was sufficient in regulating CFTR biogenesis. We identified mutations in an unstructured loop within the MSP that uncoupled VAPB-regulated CFTR biogenesis from basic interactions with FFAT. Using this information, we defined functional and physical interactions between VAPB and proteostasis regulators (ligands), including the unfolded protein response sensor ATF6 and the ER degradation cluster that included FAF1, VCP, BAP31, and Derlin-1. VAPB inhibited the degradation of ΔF508-CFTR in the ER through interactions with the RMA1-Derlin-BAP31-VCP pathway. Analysis of pseudoligands containing tandem FFAT signals supports a competitive model for VAP interactions that direct CFTR biogenesis. The results suggest a model in which VAP-ligand binding couples proteostasis and lipid homeostasis leading to observed phenotypes of lipid abnormalities in protein folding diseases.
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Registered trials
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.