Nucleosomes enter cells by clathrin- and caveolin-dependent endocytosis
| Autor: | Huawei Wang, Xiajing Shan, Mengtian Ren, Mengdi Shang, Chuanzheng Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Cholera Toxin
Microscopy Confocal AcademicSubjects/SCI00010 THP-1 Cells Cell Membrane Transferrin Golgi Apparatus Endosomes Hep G2 Cells Genome Integrity Repair and Replication Endoplasmic Reticulum Caveolins Clathrin Endocytosis Cell Line Nucleosomes Mice Genetics Animals Humans Lysosomes HeLa Cells |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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