Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus
Abstract TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates in the nucleus and cytoplasm, contributing to the onset of amyotrophic lateral sclerosis. In this study, we...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47167-x |
| _version_ | 1827291458285076480 |
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| author | Hong Zhang Huazhang Guo Danni Li Yiling Zhang Shengnan Zhang Wenyan Kang Cong Liu Weidong Le Liang Wang Dan Li Bin Dai |
| author_facet | Hong Zhang Huazhang Guo Danni Li Yiling Zhang Shengnan Zhang Wenyan Kang Cong Liu Weidong Le Liang Wang Dan Li Bin Dai |
| author_sort | Hong Zhang |
| collection | DOAJ |
| description | Abstract TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates in the nucleus and cytoplasm, contributing to the onset of amyotrophic lateral sclerosis. In this study, we evaluate the effect of graphene quantum dots (GQDs) with different functional groups on TDP-43’s phase separation and aggregation in various cellular locations. We find that halogen atom-doped GQDs (GQDs-Cl, Cl-GQDs-OH) penetrate the nuclear envelope, inhibiting the assembly of TDP-43 nuclear bodies and stress granules under oxidative stress or hyperosmotic environments, and reduce amyloid aggregates and disease-associated phosphorylation of TDP-43. Mechanistic analysis reveals GQDs-Cl and Cl-GQDs-OH modulate TDP-43 phase separation through hydrophobic and electrostatic interactions. Our findings highlight the potential of GQDs-Cl and Cl-GQDs-OH in modulating nuclear protein condensation and pathological aggregation, offering direction for the innovative design of GQDs to modulate protein phase separation and aggregation. |
| first_indexed | 2024-04-24T12:37:19Z |
| format | Article |
| id | doaj.art-6fe062fdfb2745578d25b412f7a95913 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:37:19Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj.art-6fe062fdfb2745578d25b412f7a959132024-04-07T11:24:40ZengNature PortfolioNature Communications2041-17232024-04-0115111310.1038/s41467-024-47167-xHalogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleusHong Zhang0Huazhang Guo1Danni Li2Yiling Zhang3Shengnan Zhang4Wenyan Kang5Cong Liu6Weidong Le7Liang Wang8Dan Li9Bin Dai10School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong UniversityInstitute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai UniversitySchool of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong UniversitySchool of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong UniversityInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesShanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalInstitute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai UniversityKey Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong UniversitySchool of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong UniversityAbstract TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates in the nucleus and cytoplasm, contributing to the onset of amyotrophic lateral sclerosis. In this study, we evaluate the effect of graphene quantum dots (GQDs) with different functional groups on TDP-43’s phase separation and aggregation in various cellular locations. We find that halogen atom-doped GQDs (GQDs-Cl, Cl-GQDs-OH) penetrate the nuclear envelope, inhibiting the assembly of TDP-43 nuclear bodies and stress granules under oxidative stress or hyperosmotic environments, and reduce amyloid aggregates and disease-associated phosphorylation of TDP-43. Mechanistic analysis reveals GQDs-Cl and Cl-GQDs-OH modulate TDP-43 phase separation through hydrophobic and electrostatic interactions. Our findings highlight the potential of GQDs-Cl and Cl-GQDs-OH in modulating nuclear protein condensation and pathological aggregation, offering direction for the innovative design of GQDs to modulate protein phase separation and aggregation.https://doi.org/10.1038/s41467-024-47167-x |
| spellingShingle | Hong Zhang Huazhang Guo Danni Li Yiling Zhang Shengnan Zhang Wenyan Kang Cong Liu Weidong Le Liang Wang Dan Li Bin Dai Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus Nature Communications |
| title | Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus |
| title_full | Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus |
| title_fullStr | Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus |
| title_full_unstemmed | Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus |
| title_short | Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus |
| title_sort | halogen doped graphene quantum dots modulate tdp 43 phase separation and aggregation in the nucleus |
| url | https://doi.org/10.1038/s41467-024-47167-x |
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