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Mechanism of membrane-curvature generation by ER-tubule shaping proteins

Author

Listed:
  • Ning Wang

    (Harvard Medical School)

  • Lindsay D. Clark

    (Harvard Medical School)

  • Yuan Gao

    (Harvard Medical School)

  • Michael M. Kozlov

    (Sackler Faculty of Medicine, Tel Aviv University)

  • Tom Shemesh

    (Technion-Israel Institute of Technology)

  • Tom A. Rapoport

    (Harvard Medical School)

Abstract

The endoplasmic reticulum (ER) network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs. These proteins have two pairs of trans-membrane (TM) segments, followed by an amphipathic helix (APH), but how they induce curvature is poorly understood. Here, we show that REEPs form homodimers by interaction within the membrane. When overexpressed or reconstituted at high concentrations with phospholipids, REEPs cause extreme curvature through their TMs, generating lipoprotein particles instead of vesicles. The APH facilitates curvature generation, as its mutation prevents ER network formation of reconstituted proteoliposomes, and synthetic L- or D-amino acid peptides abolish ER network formation in Xenopus egg extracts. In Schizosaccharomyces japonicus, the APH is required for reticulon’s exclusive ER-tubule localization and restricted mobility. Thus, the TMs and APH cooperate to generate high membrane curvature. We propose that the formation of splayed REEP/reticulon dimers is responsible for ER tubule formation.

Suggested Citation

  • Ning Wang & Lindsay D. Clark & Yuan Gao & Michael M. Kozlov & Tom Shemesh & Tom A. Rapoport, 2021. "Mechanism of membrane-curvature generation by ER-tubule shaping proteins," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20625-y
    DOI: 10.1038/s41467-020-20625-y
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    Cited by:

    1. Ning Wang & Yoko Shibata & Joao A. Paulo & Steven P. Gygi & Tom A. Rapoport, 2023. "A conserved membrane curvature-generating protein is crucial for autophagosome formation in fission yeast," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yoko Shibata & Emily E. Mazur & Buyan Pan & Joao A. Paulo & Steven P. Gygi & Suyog Chavan & L. Sebastian Alexis Valerio & Jiuchun Zhang & Tom A. Rapoport, 2024. "The membrane curvature-inducing REEP1-4 proteins generate an ER-derived vesicular compartment," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Yun Xiang & Rui Lyu & Junjie Hu, 2023. "Oligomeric scaffolding for curvature generation by ER tubule-forming proteins," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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