IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29077-y.html
   My bibliography  Save this article

RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning

Author

Listed:
  • Gaurav Kumar

    (CSIR-Institute of Microbial Technology (IMTECH))

  • Prateek Chawla

    (Indian Institute of Science Education and Research (IISER))

  • Neha Dhiman

    (Indian Institute of Science Education and Research (IISER))

  • Sanya Chadha

    (CSIR-Institute of Microbial Technology (IMTECH))

  • Sheetal Sharma

    (CSIR-Institute of Microbial Technology (IMTECH))

  • Kanupriya Sethi

    (CSIR-Institute of Microbial Technology (IMTECH))

  • Mahak Sharma

    (Indian Institute of Science Education and Research (IISER))

  • Amit Tuli

    (CSIR-Institute of Microbial Technology (IMTECH))

Abstract

The bidirectional movement of lysosomes on microtubule tracks regulates their whole-cell spatial arrangement. Arl8b, a small GTP-binding (G) protein, promotes lysosome anterograde trafficking mediated by kinesin-1. Herein, we report an Arl8b effector, RUFY3, which regulates the retrograde transport of lysosomes. We show that RUFY3 interacts with the JIP4-dynein-dynactin complex and facilitates Arl8b association with the retrograde motor complex. Accordingly, RUFY3 knockdown disrupts the positioning of Arl8b-positive endosomes and reduces Arl8b colocalization with Rab7-marked late endosomal compartments. Moreover, we find that RUFY3 regulates nutrient-dependent lysosome distribution, although autophagosome-lysosome fusion and autophagic cargo degradation are not impaired upon RUFY3 depletion. Interestingly, lysosome size is significantly reduced in RUFY3 depleted cells, which could be rescued by inhibition of the lysosome reformation regulatory factor PIKFYVE. These findings suggest a model in which the perinuclear cloud arrangement of lysosomes regulates both the positioning and size of these proteolytic compartments.

Suggested Citation

  • Gaurav Kumar & Prateek Chawla & Neha Dhiman & Sanya Chadha & Sheetal Sharma & Kanupriya Sethi & Mahak Sharma & Amit Tuli, 2022. "RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29077-y
    DOI: 10.1038/s41467-022-29077-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29077-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29077-y?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. Aysegul Sapmaz & Ilana Berlin & Erik Bos & Ruud H. Wijdeven & Hans Janssen & Rebecca Konietzny & Jimmy J. Akkermans & Ayse E. Erson-Bensan & Roman I. Koning & Benedikt M. Kessler & Jacques Neefjes & H, 2019. "USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    2. Rose Willett & José A. Martina & James P. Zewe & Rachel Wills & Gerald R. V. Hammond & Rosa Puertollano, 2017. "TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Eutteum Jeong & Rose Willett & Alberto Rissone & Martina Spina & Rosa Puertollano, 2024. "TMEM55B links autophagy flux, lysosomal repair, and TFE3 activation in response to oxidative stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Agnieszka A. Kendrick & Jenna R. Christensen, 2022. "Bidirectional lysosome transport: a balancing act between ARL8 effectors," Nature Communications, Nature, vol. 13(1), pages 1-3, December.
    3. Rahul Kumar & Maleeha Khan & Vincent Francis & Adriana Aguila & Gopinath Kulasekaran & Emily Banks & Peter S. McPherson, 2024. "DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Tal Keren-Kaplan & Amra Sarić & Saikat Ghosh & Chad D. Williamson & Rui Jia & Yan Li & Juan S. Bonifacino, 2022. "RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    5. Kshitiz Walia & Abhishek Sharma & Sankalita Paul & Priya Chouhan & Gaurav Kumar & Rajesh Ringe & Mahak Sharma & Amit Tuli, 2024. "SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

    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. Karin Vogel & Tobias Bläske & Marie-Kristin Nagel & Christoph Globisch & Shane Maguire & Lorenz Mattes & Christian Gude & Michael Kovermann & Karin Hauser & Christine Peter & Erika Isono, 2022. "Lipid-mediated activation of plasma membrane-localized deubiquitylating enzymes modulate endosomal trafficking," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Eutteum Jeong & Rose Willett & Alberto Rissone & Martina Spina & Rosa Puertollano, 2024. "TMEM55B links autophagy flux, lysosomal repair, and TFE3 activation in response to oxidative stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Rahul Kumar & Maleeha Khan & Vincent Francis & Adriana Aguila & Gopinath Kulasekaran & Emily Banks & Peter S. McPherson, 2024. "DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Tal Keren-Kaplan & Amra Sarić & Saikat Ghosh & Chad D. Williamson & Rui Jia & Yan Li & Juan S. Bonifacino, 2022. "RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    5. James L. Daly & Chris M. Danson & Philip A. Lewis & Lu Zhao & Sara Riccardo & Lucio Filippo & Davide Cacchiarelli & Daehoon Lee & Stephen J. Cross & Kate J. Heesom & Wen-Cheng Xiong & Andrea Ballabio , 2023. "Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health," Nature Communications, Nature, vol. 14(1), pages 1-19, 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:13:y:2022:i:1:d:10.1038_s41467-022-29077-y. 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.