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The membrane curvature-inducing REEP1-4 proteins generate an ER-derived vesicular compartment

Author

Listed:
  • Yoko Shibata

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • Emily E. Mazur

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • Buyan Pan

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • Joao A. Paulo

    (Harvard Medical School)

  • Steven P. Gygi

    (Harvard Medical School)

  • Suyog Chavan

    (Harvard Medical School)

  • L. Sebastian Alexis Valerio

    (Harvard Medical School)

  • Jiuchun Zhang

    (Harvard Medical School)

  • Tom A. Rapoport

    (Harvard Medical School
    Howard Hughes Medical Institute)

Abstract

The endoplasmic reticulum (ER) is shaped by abundant membrane curvature-generating proteins that include the REEP family member REEP5. The REEP1 subfamily, consisting of four proteins in mammals (REEP1-4), is less abundant and lack a N-terminal region. Mutations in REEP1 and REEP2 cause Hereditary Spastic Paraplegia, but the function of these four REEP proteins remains enigmatic. Here we show that REEP1-4 reside in a unique vesicular compartment and identify features that determine their localization. Mutations in REEP1-4 that compromise curvature generation, including those causing disease, relocalize the proteins to the bulk ER. These mutants interact with wild-type proteins to retain them in the ER, consistent with their autosomal-dominant disease inheritance. REEP1 vesicles contain the membrane fusogen atlastin-1, but not general ER proteins. We propose that REEP1-4 generate these vesicles themselves by budding from the ER, and that they cycle back to the ER by atlastin-mediated fusion. The vesicles may serve to regulate ER tubule dynamics.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52901-6
    DOI: 10.1038/s41467-024-52901-6
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    References listed on IDEAS

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    1. Genny Orso & Diana Pendin & Song Liu & Jessica Tosetto & Tyler J. Moss & Joseph E. Faust & Massimo Micaroni & Anastasia Egorova & Andrea Martinuzzi & James A. McNew & Andrea Daga, 2009. "Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin," Nature, Nature, vol. 460(7258), pages 978-983, August.
    2. 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.
    3. 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.
    4. Robert E. Powers & Songyu Wang & Tina Y. Liu & Tom A. Rapoport, 2017. "Reconstitution of the tubular endoplasmic reticulum network with purified components," Nature, Nature, vol. 543(7644), pages 257-260, March.
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