ArticleTraffic (Copenhagen, Denmark)2011
A nonaggregating surfactant protein C mutant is misdirected to early endosomes and disrupts phospholipid recycling.
Article in Traffic (Copenhagen, Denmark), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Lung fibrosis-associated surfactant protein A1 and C variants induce latent transforming growth factor β1 secretion in lung epithelial cells.The Journal of biological chemistry · 2013Trial
- Divergent pathways of surfactant protein C maturation for disease-associated isoforms.The Journal of biological chemistry · 2026Article
- Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms.bioRxiv : the preprint server for biology · 2025Article
- Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.JCI insight · 2025Article
- Endogenous gene editing of alveolar organoids reveals that expression of pathogenic variant SFTPC-I73T disrupts endosomal function, epithelial polarity and wound healing.bioRxiv : the preprint server for biology · 2025Article
- Targeting USP11 counteractsTheranostics · 2025Article
- Towards personalized therapies for genetic disorders of surfactant dysfunction.Seminars in fetal & neonatal medicine · 2023Review
- Genetic Variant Overlap Analysis Identifies Established and Putative Genes Involved in Pulmonary Fibrosis.International journal of molecular sciences · 2023Article
- Genetics in Idiopathic Pulmonary Fibrosis: A Clinical Perspective.Diagnostics (Basel, Switzerland) · 2022Review
- Gene Therapeutics for Surfactant Dysfunction Disorders: Targeting the Alveolar Type 2 Epithelial Cell.Human gene therapy · 2022Review
- Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant.The European respiratory journal · 2022Article
- Immunophenotyping of Acute Inflammatory Exacerbations of Lung Injury Driven by Mutant Surfactant Protein-C: A Role for Inflammatory Eosinophils.Frontiers in pharmacology · 2022Article
- Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease.Cell reports · 2021Article
- The common ABCA3American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Genetic disorders of the surfactant system: focus on adult disease.European respiratory review : an official journal of the European Respiratory Society · 2021Article
- Role of CCR2Frontiers in immunology · 2021Article
- Genetic causes of surfactant protein abnormalities.Current opinion in pediatrics · 2019Review
- In utero gene editing for monogenic lung disease.Science translational medicine · 2019Article
- Article
- Revealing the Secrets of Idiopathic Pulmonary Fibrosis.The New England journal of medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Interstitial lung disease in both children and adults has been linked to mutations in the lung-specific surfactant protein C (SFTPC) gene. Among these, the missense mutation [isoleucine to threonine at codon 73 = human surfactant protein C (hSP-C(I73T) )] accounts for ∼30% of all described SFTPC mutations. We reported previously that unlike the BRICHOS misfolding SFTPC mutants, expression of hSP-C(I73T) induces lung remodeling and alveolar lipoproteinosis without a substantial Endoplasmic Reticulum (ER) stress response or ER-mediated intrinsic apoptosis. We show here that, in contrast to its wild-type counterpart that is directly routed to lysosomal-like organelles for processing, SP-C(I73T) is misdirected to the plasma membrane and subsequently internalized to the endocytic pathway via early endosomes, leading to the accumulation of abnormally processed proSP-C isoforms. Functionally, cells expressing hSP-C(I73T) demonstrated both impaired uptake and degradation of surfactant phospholipid, thus providing a molecular mechanism for the observed lipid accumulation in patients expressing hSP-C(I73T) through the disruption of normal phospholipid recycling. Our data provide evidence for a novel cellular mechanism for conformational protein-associated diseases and suggest a paradigm for mistargeted proteins involved in the disruption of the endosomal/lysosomal sorting machinery.
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What OpenQuestion holds
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.