The role of scaffold reshaping and disassembly in dynamin driven membrane fission

  1. Martina Pannuzzo
  2. Zachary A McDargh
  3. Markus Deserno  Is a corresponding author
  1. Carnegie Mellon University, United States

Abstract

The large GTPase dynamin catalyzes membrane fission in eukaryotic cells, but despite three decades of experimental work, competing and partially conflicting models persist regarding some of its most basic actions. Here we investigate the mechanical and functional consequences of dynamin scaffold shape changes and disassembly with the help of a geometrically and elastically realistic simulation model of helical dynamin-membrane complexes. Beyond changes of radius and pitch, we emphasize the crucial role of a third functional motion: an effective rotation of the filament around its longitudinal axis, which reflects alternate tilting of dynamin's PH binding domains and creates a membrane torque. We also show that helix elongation impedes fission, hemifission is reached via a small transient pore, and coat disassembly assists fission. Our results have several testable structural consequences and help to reconcile mutual conflicting aspects between the two main present models of dynamin fission-the two-stage and the constrictase model.

Data availability

The simulation software used is freely available at http://espressomd.org/wordpress/. Source data for Figure 2F, the supplement figure to Figure 2F, Figure 3, and Figure 6 are also provided.

Article and author information

Author details

  1. Martina Pannuzzo

    Department of Physics, Carnegie Mellon University, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zachary A McDargh

    Department of Physics, Carnegie Mellon University, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Markus Deserno

    Department of Physics, Carnegie Mellon University, Pittsburgh, United States
    For correspondence
    deserno@andrew.cmu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5692-1595

Funding

National Science Foundation (NSF CHE #1464926)

  • Markus Deserno

Carnegie Mellon University (Center of Excellence funding)

  • Markus Deserno

European Union Horizon 2020 Research and Innovation Program (Marie Sklodowska-Curie grant agreement no. 754490)

  • Martina Pannuzzo

National Science Foundation (NSF CHE #1764257)

  • Markus Deserno

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

Copyright

© 2018, Pannuzzo 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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  1. Martina Pannuzzo
  2. Zachary A McDargh
  3. Markus Deserno
(2018)
The role of scaffold reshaping and disassembly in dynamin driven membrane fission
eLife 7:e39441.
https://doi.org/10.7554/eLife.39441

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https://doi.org/10.7554/eLife.39441