IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39700-1.html
   My bibliography  Save this article

Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers

Author

Listed:
  • Meghan Lee Arnold

    (Rutgers University)

  • Jason Cooper

    (Rutgers University)

  • Rebecca Androwski

    (Rutgers University)

  • Sohil Ardeshna

    (Rutgers University)

  • Ilija Melentijevic

    (Rutgers University)

  • Joelle Smart

    (Rutgers University)

  • Ryan J. Guasp

    (Rutgers University)

  • Ken C. Q. Nguyen

    (Rose F. Kennedy Center)

  • Ge Bai

    (Rutgers University)

  • David H. Hall

    (Rose F. Kennedy Center)

  • Barth D. Grant

    (Rutgers University)

  • Monica Driscoll

    (Rutgers University)

Abstract

Toxic protein aggregates can spread among neurons to promote human neurodegenerative disease pathology. We found that in C. elegans touch neurons intermediate filament proteins IFD-1 and IFD-2 associate with aggresome-like organelles and are required cell-autonomously for efficient production of neuronal exophers, giant vesicles that can carry aggregates away from the neuron of origin. The C. elegans aggresome-like organelles we identified are juxtanuclear, HttPolyQ aggregate-enriched, and dependent upon orthologs of mammalian aggresome adaptor proteins, dynein motors, and microtubule integrity for localized aggregate collection. These key hallmarks indicate that conserved mechanisms drive aggresome formation. Furthermore, we found that human neurofilament light chain (NFL) can substitute for C. elegans IFD-2 in promoting exopher extrusion. Taken together, our results suggest a conserved influence of intermediate filament association with aggresomes and neuronal extrusions that eject potentially toxic material. Our findings expand understanding of neuronal proteostasis and suggest implications for neurodegenerative disease progression.

Suggested Citation

  • Meghan Lee Arnold & Jason Cooper & Rebecca Androwski & Sohil Ardeshna & Ilija Melentijevic & Joelle Smart & Ryan J. Guasp & Ken C. Q. Nguyen & Ge Bai & David H. Hall & Barth D. Grant & Monica Driscoll, 2023. "Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39700-1
    DOI: 10.1038/s41467-023-39700-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39700-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39700-1?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. Nicholas J. Ashton & Shorena Janelidze & Ahmad Al Khleifat & Antoine Leuzy & Emma L. van der Ende & Thomas K. Karikari & Andrea L. Benedet & Tharick A. Pascoal & Alberto Lleó & Lucilla Parnetti & Dani, 2021. "A multicentre validation study of the diagnostic value of plasma neurofilament light," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Ilija Melentijevic & Marton L. Toth & Meghan L. Arnold & Ryan J. Guasp & Girish Harinath & Ken C. Nguyen & Daniel Taub & J. Alex Parker & Christian Neri & Christopher V. Gabel & David H. Hall & Monica, 2017. "C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress," Nature, Nature, vol. 542(7641), pages 367-371, February.
    3. Mohammed D. Aljohani & Sonia El Mouridi & Monika Priyadarshini & Amhed M. Vargas-Velazquez & Christian Frøkjær-Jensen, 2020. "Engineering rules that minimize germline silencing of transgenes in simple extrachromosomal arrays in C. elegans," Nature Communications, Nature, vol. 11(1), pages 1-14, 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. Qiang Zhu & Matthew E. Combs & Juan Liu & Xue Bai & Wenbo B. Wang & Laura E. Herring & Jiandong Liu & Jason W. Locasale & Dawn E. Bowles & Ryan T. Gross & Michelle Mendiola Pla & Christopher P. Mack &, 2023. "GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Agata Szczepańska & Katarzyna Olek & Klaudia Kołodziejska & Jingfang Yu & Abdulrahman Tudu Ibrahim & Laura Adamkiewicz & Frank C. Schroeder & Wojciech Pokrzywa & Michał Turek, 2024. "Pheromone-based communication influences the production of somatic extracellular vesicles in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Arthur Fischbach & Angela Johns & Kara L. Schneider & Xinxin Hao & Peter Tessarz & Thomas Nyström, 2023. "Artificial Hsp104-mediated systems for re-localizing protein aggregates," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Wang Yuan & Yi M. Weaver & Svetlana Earnest & Clinton A. Taylor & Melanie H. Cobb & Benjamin P. Weaver, 2023. "Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Lasse Dissing-Olesen & Alec J. Walker & Qian Feng & Helena J. Barr & Alicia C. Walker & Lili Xie & Daniel K. Wilton & Indrani Das & Larry I. Benowitz & Beth Stevens, 2023. "FEAST: A flow cytometry-based toolkit for interrogating microglial engulfment of synaptic and myelin proteins," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Hayden Weng Siong Tan & Guang Lu & Han Dong & Yik-Lam Cho & Auginia Natalia & Liming Wang & Charlene Chan & Dennis Kappei & Reshma Taneja & Shuo-Chien Ling & Huilin Shao & Shih-Yin Tsai & Wen-Xing Din, 2022. "A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Wenjing Liang & Shakti Sagar & Rishith Ravindran & Rita H. Najor & Justin M. Quiles & Liguo Chi & Rachel Y. Diao & Benjamin P. Woodall & Leonardo J. Leon & Erika Zumaya & Jason Duran & David M. Cauvi , 2023. "Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Fernando Gonzalez-Ortiz & Bjørn-Eivind Kirsebom & José Contador & Jordan E. Tanley & Per Selnes & Berglind Gísladóttir & Lene Pålhaugen & Mathilde Suhr Hemminghyth & Jonas Jarholm & Ragnhild Skogseth , 2024. "Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-13, 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:14:y:2023:i:1:d:10.1038_s41467-023-39700-1. 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.