IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59605-5.html
   My bibliography  Save this article

Autophagy-independent role of ATG9A vesicles as carriers for galectin-9 secretion

Author

Listed:
  • Wenting Zhang

    (Beijing University of Technology)

  • Cuicui Ji

    (Beijing University of Technology)

  • Xianghua Li

    (Beijing University of Technology)

  • Tianlong He

    (Beijing University of Technology)

  • Wei Jiang

    (Beijing University of Technology)

  • Yukun Liu

    (Beijing University of Technology)

  • Meiling Wu

    (Beijing University of Technology)

  • Yunpeng Zhao

    (Beijing University of Technology)

  • Xuechai Chen

    (Beijing University of Technology)

  • Xiaoli Wang

    (Beijing University of Technology)

  • Jian Li

    (Shandong University)

  • Haolin Zhang

    (Beijing University of Technology)

  • Juan Wang

    (Beijing University of Technology)

Abstract

Galectins play vital roles in cellular processes such as adhesion, communication, and survival, yet the mechanisms underlying their unconventional secretion remain poorly understood. This study identifies ATG9A, a core autophagy protein, as a key regulator of galectin-9 secretion via a mechanism independent of classical autophagy, secretory autophagy, or the LC3-dependent extracellular vesicle loading and secretion pathway. ATG9A vesicles function as specialized carriers, with the N-terminus of ATG9A and both carbohydrate recognition domains of galectin-9 being critical for the process. TMED10 mediates the incorporation of galectin-9 into ATG9A vesicles, which then fuse with the plasma membrane via the STX13-SNAP23-VAMP3 SNARE complex. Furthermore, ATG9A regulates the secretion of other proteins, including galectin-4, galectin-8, and annexin A6, but not IL-1β, galectin-3, or FGF2. This mechanism is potentially conserved across other cell types, including monocytic cells, which underscores its broader significance in unconventional protein secretion.

Suggested Citation

  • Wenting Zhang & Cuicui Ji & Xianghua Li & Tianlong He & Wei Jiang & Yukun Liu & Meiling Wu & Yunpeng Zhao & Xuechai Chen & Xiaoli Wang & Jian Li & Haolin Zhang & Juan Wang, 2025. "Autophagy-independent role of ATG9A vesicles as carriers for galectin-9 secretion," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59605-5
    DOI: 10.1038/s41467-025-59605-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59605-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59605-5?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-59605-5. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.