ArticleNucleic acids research2021
Nucleosomes enter cells by clathrin- and caveolin-dependent endocytosis.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Integrative genomics and structural bioinformatics uncovers AMR-associated drug targets and pqsH inhibitors in multidrug-resistant Pseudomonas aeruginosa JJPA01.Molecular diversity · 2026Article
- Bidirectional Interactions Between Nanomaterials and Extracellular Vesicles: Molecular Insights and Translational Implications.International journal of nanomedicine · 2026Review
- Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.Frontiers in pharmacology · 2025Review
- Endocytosis and non-canonical autophagy mediate extracellular histones cytotoxicity in vascular models of sepsis.Frontiers in immunology · 2025Article
- Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.Biomedicines · 2024Article
- LY6K depletion modulates TGF-β and EGF signaling.Cancer medicine · 2023Article
- Extracellular Histones Activate Endothelial NLRP3 Inflammasome and are Associated with a Severe Sepsis Phenotype.Journal of inflammation research · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage and apoptosis lead to the release of free nucleosomes-the basic structural repeating units of chromatin-into the blood circulation system. We recently reported that free nucleosomes that enter the cytoplasm of mammalian cells trigger immune responses by activating cGMP-AMP synthase (cGAS). In the present study, we designed experiments to reveal the mechanism of nucleosome uptake by human cells. We showed that nucleosomes are first absorbed on the cell membrane through nonspecific electrostatic interactions between positively charged histone N-terminal tails and ligands on the cell surface, followed by internalization via clathrin- or caveolae-dependent endocytosis. After cellular internalization, endosomal escape occurs rapidly, and nucleosomes are released into the cytosol, maintaining structural integrity for an extended period. The efficient endocytosis of extracellular nucleosomes suggests that circulating nucleosomes may lead to cellular disorders as well as immunostimulation, and thus, the biological effects exerted by endocytic nucleosomes should be addressed in the future.
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