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Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector

Author

Listed:
  • Amrita Rai

    (Max Planck Institute of Molecular Physiology)

  • Anurag K. Singh

    (Martin Luther University Halle-Wittenberg)

  • Nathalie Bleimling

    (Max Planck Institute of Molecular Physiology)

  • Guido Posern

    (Martin Luther University Halle-Wittenberg)

  • Ingrid R. Vetter

    (Max Planck Institute of Molecular Physiology)

  • Roger S. Goody

    (Max Planck Institute of Molecular Physiology)

Abstract

In their GTP-bound (active) form, Rab proteins interact with effector proteins that control downstream signaling. One such Rab15 effector is Rep15, which is known to have a role in receptor recycling from the endocytic recycling compartment but otherwise remains poorly characterized. Here, we report the characterization of the Rep15:Rab15 interaction and identification of Rab3 paralogs and Rab34 as Rep15 interacting partners from a yeast two-hybrid assay. Biochemical validation of the interactions is presented and crystal structures of the Rep15:Rab3B and Rep15:Rab3C complexes provide additional mechanistic insight. We find that Rep15 adopts a globular structure that is distinct from other reported Rab15, Rab3 and Rab34 effectors. Structure-based mutagenesis experiments explain the Rep15:Rab interaction specificity. Rep15 depletion in U138MG glioblastoma cells impairs cell proliferation, cell migration and receptor recycling, underscoring the need for further clarification of the role of Rep15 in cancer.

Suggested Citation

  • Amrita Rai & Anurag K. Singh & Nathalie Bleimling & Guido Posern & Ingrid R. Vetter & Roger S. Goody, 2022. "Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31831-1
    DOI: 10.1038/s41467-022-31831-1
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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Yun Wang & Masaya Okamoto & Frank Schmitz & Kay Hofmann & Thomas C. Südhof, 1997. "Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion," Nature, Nature, vol. 388(6642), pages 593-598, August.
    3. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    4. Amrita Rai & Nathalie Bleimling & Ingrid R. Vetter & Roger S. Goody, 2020. "The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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