IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47167-x.html
   My bibliography  Save this article

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

Author

Listed:
  • Hong Zhang

    (Shanghai Jiao Tong University)

  • Huazhang Guo

    (Shanghai University)

  • Danni Li

    (Shanghai Jiao Tong University)

  • Yiling Zhang

    (Shanghai Jiao Tong University)

  • Shengnan Zhang

    (Chinese Academy of Sciences)

  • Wenyan Kang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine (Boao Research Hospital))

  • Cong Liu

    (Chinese Academy of Sciences)

  • Weidong Le

    (Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital
    Shanghai University of Medicine and Health Sciences)

  • Liang Wang

    (Shanghai University)

  • Dan Li

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Bin Dai

    (Shanghai Jiao Tong University)

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.

Suggested Citation

  • Hong Zhang & Huazhang Guo & Danni Li & Yiling Zhang & Shengnan Zhang & Wenyan Kang & Cong Liu & Weidong Le & Liang Wang & Dan Li & Bin Dai, 2024. "Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47167-x
    DOI: 10.1038/s41467-024-47167-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47167-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-47167-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jorge Garcia Morato & Friederike Hans & Felix Zweydorf & Regina Feederle & Simon J. Elsässer & Angelos A. Skodras & Christian Johannes Gloeckner & Emanuele Buratti & Manuela Neumann & Philipp J. Kahle, 2022. "Sirtuin-1 sensitive lysine-136 acetylation drives phase separation and pathological aggregation of TDP-43," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Georg Krainer & Timothy J. Welsh & Jerelle A. Joseph & Jorge R. Espinosa & Sina Wittmann & Ella Csilléry & Akshay Sridhar & Zenon Toprakcioglu & Giedre Gudiškytė & Magdalena A. Czekalska & William E. , 2021. "Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. W. Michael Babinchak & Benjamin K. Dumm & Sarah Venus & Solomiia Boyko & Andrea A. Putnam & Eckhard Jankowsky & Witold K. Surewicz, 2020. "Small molecules as potent biphasic modulators of protein liquid-liquid phase separation," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. William E. Arter & Runzhang Qi & Nadia A. Erkamp & Georg Krainer & Kieran Didi & Timothy J. Welsh & Julia Acker & Jonathan Nixon-Abell & Seema Qamar & Jordina Guillén-Boixet & Titus M. Franzmann & Dav, 2022. "Biomolecular condensate phase diagrams with a combinatorial microdroplet platform," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Ashish Joshi & Anuja Walimbe & Snehasis Sarkar & Lisha Arora & Gaganpreet Kaur & Prince Jhandai & Dhruba Chatterjee & Indranil Banerjee & Samrat Mukhopadhyay, 2024. "Intermolecular energy migration via homoFRET captures the modulation in the material property of phase-separated biomolecular condensates," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Aishwarya Agarwal & Lisha Arora & Sandeep K. Rai & Anamika Avni & Samrat Mukhopadhyay, 2022. "Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Hema M. Swasthi & Joseph L. Basalla & Claire E. Dudley & Anthony G. Vecchiarelli & Matthew R. Chapman, 2023. "Cell surface-localized CsgF condensate is a gatekeeper in bacterial curli subunit secretion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Georg Krainer & Kadi L. Saar & William E. Arter & Timothy J. Welsh & Magdalena A. Czekalska & Raphaël P. B. Jacquat & Quentin Peter & Walther C. Traberg & Arvind Pujari & Akhila K. Jayaram & Pavankuma, 2023. "Direct digital sensing of protein biomarkers in solution," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Manisha Poudyal & Komal Patel & Laxmikant Gadhe & Ajay Singh Sawner & Pradeep Kadu & Debalina Datta & Semanti Mukherjee & Soumik Ray & Ambuja Navalkar & Siddhartha Maiti & Debdeep Chatterjee & Jyoti D, 2023. "Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    7. Andrew Z. Lin & Kiersten M. Ruff & Furqan Dar & Ameya Jalihal & Matthew R. King & Jared M. Lalmansingh & Ammon E. Posey & Nadia A. Erkamp & Ian Seim & Amy S. Gladfelter & Rohit V. Pappu, 2023. "Dynamical control enables the formation of demixed biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Avigail Baruch Leshem & Sian Sloan-Dennison & Tlalit Massarano & Shavit Ben-David & Duncan Graham & Karen Faulds & Hugo E. Gottlieb & Jordan H. Chill & Ayala Lampel, 2023. "Biomolecular condensates formed by designer minimalistic peptides," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Fang Wu & Natali H. Muskat & Inbar Dvilansky & Omri Koren & Anat Shahar & Roi Gazit & Natalie Elia & Eyal Arbely, 2023. "Acetylation-dependent coupling between G6PD activity and apoptotic signaling," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Bikash Chandra Swain & Pascale Sarkis & Vanessa Ung & Sabrina Rousseau & Laurent Fernandez & Ani Meltonyan & V. Esperance Aho & Davide Mercadante & Cameron D. Mackereth & Mikayel Aznauryan, 2024. "Disordered regions of human eIF4B orchestrate a dynamic self-association landscape," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. David Q. P. Reis & Sara Pereira & Ana P. Ramos & Pedro M. Pereira & Leonor Morgado & Joana Calvário & Adriano O. Henriques & Mónica Serrano & Ana S. Pina, 2024. "Catalytic peptide-based coacervates for enhanced function through structural organization and substrate specificity," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    12. Yuri Hong & Saeed Najafi & Thomas Casey & Joan-Emma Shea & Song-I Han & Dong Soo Hwang, 2022. "Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Andres R. Tejedor & Ignacio Sanchez-Burgos & Maria Estevez-Espinosa & Adiran Garaizar & Rosana Collepardo-Guevara & Jorge Ramirez & Jorge R. Espinosa, 2022. "Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Xi Li & Linwei Yu & Xikai Liu & Tianyi Shi & Yu Zhang & Yushuo Xiao & Chen Wang & Liangliang Song & Ning Li & Xinran Liu & Yuchen Chen & Robert B. Petersen & Xiang Cheng & Weikang Xue & Yanxun V. Yu &, 2024. "β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Tomas Sneideris & Nadia A. Erkamp & Hannes Ausserwöger & Kadi L. Saar & Timothy J. Welsh & Daoyuan Qian & Kai Katsuya-Gaviria & Margaret L. L. Y. Johncock & Georg Krainer & Alexander Borodavka & Tuoma, 2023. "Targeting nucleic acid phase transitions as a mechanism of action for antimicrobial peptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Tuan Nguyen & Sai Li & Jeremy T-H Chang & John W. Watters & Htet Ng & Adewola Osunsade & Yael David & Shixin Liu, 2022. "Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    17. Saumyak Mukherjee & Lars V. Schäfer, 2023. "Thermodynamic forces from protein and water govern condensate formation of an intrinsically disordered protein domain," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    18. Georg Krainer & Raphael P. B. Jacquat & Matthias M. Schneider & Timothy J. Welsh & Jieyuan Fan & Quentin A. E. Peter & Ewa A. Andrzejewska & Greta Šneiderienė & Magdalena A. Czekalska & Hannes Ausserw, 2024. "Single-molecule digital sizing of proteins in solution," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Daniel C. Carrettiero & Maria C. Almeida & Andrew P. Longhini & Jennifer N. Rauch & Dasol Han & Xuemei Zhang & Saeed Najafi & Jason E. Gestwicki & Kenneth S. Kosik, 2022. "Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    20. Chenyang Lan & Juhyeong Kim & Svenja Ulferts & Fernando Aprile-Garcia & Sophie Weyrauch & Abhinaya Anandamurugan & Robert Grosse & Ritwick Sawarkar & Aleks Reinhardt & Thorsten Hugel, 2023. "Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation," Nature Communications, Nature, vol. 14(1), pages 1-8, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47167-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.