ArticleThe Journal of cell biology2020
Heparan sulfate is a clearance receptor for aberrant extracellular proteins.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 58 citations in OpenAlex.
- GPLD1 is a scavenger carrier mediating lysosomal degradation of extracellular aberrant proteins.Life science alliance · 2026Article
- Article
- Quantifying Lysosomal Degradation of Extracellular Proteins With a Fluorescent Protein-Based Internalization Assay.Bio-protocol · 2026Article
- Structural analyses define the molecular basis of clusterin chaperone function.Nature structural & molecular biology · 2025Article
- Article
- Clusterin: structure, function and roles in disease.International journal of medical sciences · 2025Review
- Clusterin is a Potential Therapeutic Target in Alzheimer's Disease.Molecular neurobiology · 2024Review
- The secreted host-cell protein clusterin interacts with PmpD and promotesFrontiers in cellular and infection microbiology · 2024Article
- Clinical significance of exostosin 1 in confirmed and suspected lupus membranous nephropathy.Lupus science & medicine · 2023Article
- Extracellular protein homeostasis in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins.Scientific reports · 2023Article
- Analysis of the Expression of Exostosins and Clinicopathological Features in Membranous Lupus Nephritis in a Chinese Cohort.Kidney international reports · 2022Article
- Novel insight into the role of clusterin on intraocular pressure regulation by modifying actin polymerization and extracellular matrix remodeling in the trabecular meshwork.Journal of cellular physiology · 2022Article
- Lipoproteins in the Central Nervous System: From Biology to Pathobiology.Annual review of biochemistry · 2022Review
- Stress-responsive regulation of extracellular proteostasis.The Journal of cell biology · 2022Review
- Polyphosphate in Antiviral Protection: A Polyanionic Inorganic Polymer in the Fight Against Coronavirus SARS-CoV-2 Infection.Progress in molecular and subcellular biology · 2022Article
- Protocol for quantification of the lysosomal degradation of extracellular proteins into mammalian cells.STAR protocols · 2021Article
- Structural basis of soluble membrane attack complex packaging for clearance.Nature communications · 2021Article
- Chemical Modification of Glycosaminoglycan Polysaccharides.Molecules (Basel, Switzerland) · 2021Review
- The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model.Nature communications · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The accumulation of aberrant proteins leads to various neurodegenerative disorders. Mammalian cells contain several intracellular protein degradation systems, including autophagy and proteasomal systems, that selectively remove aberrant intracellular proteins. Although mammals contain not only intracellular but also extracellular proteins, the mechanism underlying the quality control of aberrant extracellular proteins is poorly understood. Here, using a novel quantitative fluorescence assay and genome-wide CRISPR screening, we identified the receptor-mediated degradation pathway by which misfolded extracellular proteins are selectively captured by the extracellular chaperone Clusterin and undergo endocytosis via the cell surface heparan sulfate (HS) receptor. Biochemical analyses revealed that positively charged residues on Clusterin electrostatically interact with negatively charged HS. Furthermore, the Clusterin-HS pathway facilitates the degradation of amyloid β peptide and diverse leaked cytosolic proteins in extracellular space. Our results identify a novel protein quality control system for preserving extracellular proteostasis and highlight its role in preventing diseases associated with aberrant extracellular proteins.
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What Socratic 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 Socratic graph.