1. Structural Biology and Molecular Biophysics
  2. Cell Biology
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Structural inhibition of dynamin-mediated membrane fission by endophilin

  1. Annika Hohendahl
  2. Nathaniel Talledge
  3. Valentina Galli
  4. Peter S Shen
  5. Frédéric Humbert
  6. Pietro De Camilli
  7. Adam Frost  Is a corresponding author
  8. Aurélien Roux  Is a corresponding author
  1. University of Geneva, Switzerland
  2. University of California, San Francisco, United States
  3. University of Utah, United States
  4. Howard Hughes Medical Institute, Yale University School of Medicine, United States
Research Article
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Cite this article as: eLife 2017;6:e26856 doi: 10.7554/eLife.26856

Abstract

Dynamin, which mediates membrane fission during endocytosis, binds endophilin and other members of the Bin-Amphiphysin-Rvs (BAR) protein family. How endophilin influences endocytic membrane fission is still unclear. Here we show that dynamin-mediated membrane fission is potently inhibited in vitro when an excess of endophilin co-assembles with dynamin around membrane tubules. We further show by electron microscopy that endophilin intercalates between turns of the dynamin helix and impairs fission by preventing trans interactions between dynamin rungs that are thought to play critical roles in membrane constriction. In living cells, overexpression of endophilin delayed both fission and transferrin uptake. Together, our observations suggest that while endophilin helps shape endocytic tubules and recruit dynamin to endocytic sites, it can also block membrane fission when present in excess by inhibiting inter-dynamin interactions. The sequence of recruitment and the relative stoichiometry of the two proteins may be critical to regulated endocytic fission.

Article and author information

Author details

  1. Annika Hohendahl

    Department of Biochemistry, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Nathaniel Talledge

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Valentina Galli

    Department of Biochemistry, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Peter S Shen

    Department of Biochemistry, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Frédéric Humbert

    Department of Biochemistry, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Pietro De Camilli

    Department of Neuroscience, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Adam Frost

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    For correspondence
    adam.frost@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2231-2577
  8. Aurélien Roux

    Department of Biochemistry, University of Geneva, Geneva, Switzerland
    For correspondence
    aurelien.roux@unige.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6088-0711

Funding

H2020 European Research Council (311536)

  • Aurélien Roux

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_130520)

  • Aurélien Roux

Human Frontier Science Program (CDA-0061-08)

  • Aurélien Roux

National Institutes of Health (1DP2GM110772-01)

  • Adam Frost

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_149975)

  • Aurélien Roux

Howard Hughes Medical Institute (55108523)

  • Pietro De Camilli

Searle scholars award (13SSP218)

  • Adam Frost

National Institutes of Health (NS036251)

  • Pietro De Camilli

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jenny Hinshaw, National Institutes of Health, United States

Publication history

  1. Received: March 16, 2017
  2. Accepted: September 20, 2017
  3. Accepted Manuscript published: September 21, 2017 (version 1)
  4. Version of Record published: October 31, 2017 (version 2)

Copyright

© 2017, Hohendahl et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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