ArticleProceedings of the National Academy of Sciences of the United States of America2021
Assembly and organization of the N-terminal region of mucin MUC5AC: Indications for structural and functional distinction from MUC5B.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Effectiveness of biologics for reducing occlusive mucus plugs in patients with severe asthma: a systematic review.Respiratory research · 2026Pooled it
- MUC5B and MUC5AC function in combination to regulate mucociliary transport on human airway epithelium.bioRxiv : the preprint server for biology · 2026Article
- Mucins and Respiratory Virus Infection.Annual review of virology · 2026Review
- Stretching Mucins: Exploring the Complex Rheology of a Natural Glycoprotein Network.ACS macro letters · 2026Article
- A SNP altering the MUC5AC mucin structure is increased in idiopathic pulmonary fibrosis together with the MUC5B SNP.Respiratory research · 2026Article
- An Inverse Transwell Assay for Airway Mucus Barrier Function Reveals both Virus- and Mucin-Specific Impacts on Infection.bioRxiv : the preprint server for biology · 2026Article
- GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.Cell reports · 2026Article
- Modeling chronic infection withInfection and immunity · 2026Article
- Mucoactive Agents in Muco-Obstructive Lung Diseases: A Critical Reappraisal of Pharmacological Effects and Clinical Outcomes.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- A Quantitative Lung Mucin Score to Identify Chronic Bronchitis.NEJM evidence · 2026Article
- A Coarse-Grained MARTINI Model for Mucins.Journal of chemical theory and computation · 2026Article
- Airway epithelial dysfunction in asthma pathogenesis: epigenetic mechanisms, inflammatory crosstalk, and therapeutic opportunities.Frontiers in allergy · 2026Review
- Research progress on the mechanisms of mucus retention after mycoplasma pneumoniae infection.Frontiers in cellular and infection microbiology · 2026Review
- Plastic bronchitis: a narrative review of the classification methods and pathogenesis.Frontiers in pediatrics · 2026Review
- The Application and Challenges of Stem Cell-Derived Extracellular Vesicles in Inhalation Lung Injury.International journal of nanomedicine · 2026Review
- Integrated multi-omics profiling for risk stratification in Asians with COPD.Respiratory research · 2025Article
- Highly Branched Sulfated Glycopolymers as Mucin Mimetics.Journal of the American Chemical Society · 2025Article
- Liquiritin Suppresses Intracellular and Secreted MUC5AC and MUC5B in Human Airway Epithelial Cells.International journal of molecular sciences · 2025Article
- [Protective effect ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Elevated levels of MUC5AC, one of the major gel-forming mucins in the lungs, are closely associated with chronic obstructive lung diseases such as chronic bronchitis and asthma. It is not known, however, how the structure and/or gel-making properties of MUC5AC contribute to innate lung defense in health and drive the formation of stagnant mucus in disease. To understand this, here we studied the biophysical properties and macromolecular assembly of MUC5AC compared to MUC5B. To study each native mucin, we used Calu3 monomucin cultures that produced MUC5AC or MUC5B. To understand the macromolecular assembly of MUC5AC through N-terminal oligomerization, we expressed a recombinant whole N-terminal domain (5ACNT). Scanning electron microscopy and atomic force microscopy imaging indicated that the two mucins formed distinct networks on epithelial and experimental surfaces; MUC5B formed linear, infrequently branched multimers, whereas MUC5AC formed tightly organized networks with a high degree of branching. Quartz crystal microbalance-dissipation monitoring experiments indicated that MUC5AC bound significantly more to hydrophobic surfaces and was stiffer and more viscoelastic as compared to MUC5B. Light scattering analysis determined that 5ACNT primarily forms disulfide-linked covalent dimers and higher-order oligomers (i.e., trimers and tetramers). Selective proteolytic digestion of the central glycosylated region of the full-length molecule confirmed that MUC5AC forms dimers and higher-order oligomers through its N terminus. Collectively, the distinct N-terminal organization of MUC5AC may explain the more adhesive and unique viscoelastic properties of branched, highly networked MUC5AC gels. These properties may generate insight into why/how MUC5AC forms a static, "tethered" mucus layer in chronic muco-obstructive lung diseases.
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Registered trials
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