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TUG protein acts through a disordered region to organize the early secretory pathway

Author

Listed:
  • Anup Parchure

    (Yale School of Medicine
    Yale School of Medicine)

  • Helen Tejada

    (Yale School of Medicine)

  • Zhiqun Xi

    (Yale School of Medicine)

  • Yeongho Kim

    (Yale School of Medicine)

  • Maohan Su

    (Yale School of Medicine)

  • You Yan

    (Institut Jacques Monod)

  • Omar Julca-Zevallos

    (Yale School of Medicine
    Yale School of Medicine
    LLC)

  • Abel R. Alcázar-Román

    (Yale School of Medicine
    Heinrich-Heine-University)

  • Marie Villemeur

    (Institut Jacques Monod)

  • Xinran Liu

    (Yale School of Medicine)

  • Derek Toomre

    (Yale School of Medicine)

  • Ishier Raote

    (Institut Jacques Monod)

  • Jonathan S. Bogan

    (Yale School of Medicine
    Yale School of Medicine
    Yale School of Medicine)

Abstract

The Endoplasmic Reticulum (ER)-Golgi Intermediate Compartment (ERGIC) is a network of tubules and vesicles known for producing COPI vesicles and receiving COPII vesicles from the ER. Much about its identity, stability, and regulation remains unknown. Here, we show that TUG (UBXN9, Aspscr1) protein, a central regulator of GLUT4 trafficking, localizes to the ERGIC, and that its deletion enhances anterograde flux of a model soluble cargo protein. TUG deletion redistributes ERGIC markers to the cis-Golgi and alters Golgi morphology. TUG forms biomolecular condensates in vitro and contains a central disordered region that mediates its recruitment to ERGIC membranes. A distinct N-terminal region mediates its oligomerization in cells. TUG deletion disrupts ERGIC-dependent processes, including autophagy and collagen secretion, and alters the targeting of the CFTR chloride channel. We conclude that TUG organizes and stabilizes ERGIC membranes to support their roles in diverse secretory and degradative membrane trafficking pathways.

Suggested Citation

  • Anup Parchure & Helen Tejada & Zhiqun Xi & Yeongho Kim & Maohan Su & You Yan & Omar Julca-Zevallos & Abel R. Alcázar-Román & Marie Villemeur & Xinran Liu & Derek Toomre & Ishier Raote & Jonathan S. Bo, 2025. "TUG protein acts through a disordered region to organize the early secretory pathway," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60691-8
    DOI: 10.1038/s41467-025-60691-8
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