Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus

Hong Zhang, Huazhang Guo, Danni Li, Yiling Zhang, Shengnan Zhang, Wenyan Kang, Cong Liu, Weidong Le, Liang Wang, Dan Li, Bin Dai

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number2980
Pages (from-to)2980
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Apr 6 2024

Keywords

  • Humans
  • Graphite
  • Phase Separation
  • Quantum Dots
  • Amyotrophic Lateral Sclerosis/metabolism
  • DNA-Binding Proteins/metabolism

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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