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The K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper

Author

Listed:
  • Jonas C. Alvim

    (University of Leeds
    University of Glasgow)

  • Robert M. Bolt

    (University of Leeds)

  • Jing An

    (University of Leeds)

  • Yasuko Kamisugi

    (University of Leeds)

  • Andrew Cuming

    (University of Leeds)

  • Fernanda A. L. Silva-Alvim

    (University of Leeds
    University of Glasgow)

  • Juan O. Concha

    (University of São Paulo, Ribeirão Preto)

  • Luis L. P. daSilva

    (University of São Paulo, Ribeirão Preto)

  • Meiyi Hu

    (University of Leeds)

  • Dominique Hirsz

    (University of Leeds)

  • Jurgen Denecke

    (University of Leeds)

Abstract

Accurately measuring the ability of the K/HDEL receptor (ERD2) to retain the ER cargo Amy-HDEL has questioned earlier results on which the popular receptor recycling model is based upon. Here we demonstrate that ERD2 Golgi-retention, rather than fast ER export supports its function. Ligand-induced ERD2 redistribution is only observed when the C-terminus is masked or mutated, compromising the signal that prevents Golgi-to-ER transport of the receptor. Forcing COPI mediated retrograde transport destroys receptor function, but introducing ER-to-Golgi export or cis-Golgi retention signals re-activate ERD2 when its endogenous Golgi-retention signal is masked or deleted. We propose that ERD2 remains fixed as a Golgi gatekeeper, capturing K/HDEL proteins when they arrive and releasing them again into a subdomain for retrograde transport back to the ER. An in vivo ligand:receptor ratio far greater than 100 to 1 strongly supports this model, and the underlying mechanism appears to be extremely conserved across kingdoms.

Suggested Citation

  • Jonas C. Alvim & Robert M. Bolt & Jing An & Yasuko Kamisugi & Andrew Cuming & Fernanda A. L. Silva-Alvim & Juan O. Concha & Luis L. P. daSilva & Meiyi Hu & Dominique Hirsz & Jurgen Denecke, 2023. "The K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37056-0
    DOI: 10.1038/s41467-023-37056-0
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    References listed on IDEAS

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    1. Yan Xu & Yuyong Tao & Lily S. Cheung & Chao Fan & Li-Qing Chen & Sophia Xu & Kay Perry & Wolf B. Frommer & Liang Feng, 2014. "Structures of bacterial homologues of SWEET transporters in two distinct conformations," Nature, Nature, vol. 515(7527), pages 448-452, November.
    2. Yongchan Lee & Tomohiro Nishizawa & Keitaro Yamashita & Ryuichiro Ishitani & Osamu Nureki, 2015. "Structural basis for the facilitative diffusion mechanism by SemiSWEET transporter," Nature Communications, Nature, vol. 6(1), pages 1-8, May.
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    Cited by:

    1. Fernando Aniento & David G. Robinson, 2024. "Does the KDEL receptor cycle between the Golgi and the ER?," Nature Communications, Nature, vol. 15(1), pages 1-3, December.

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