Structural inhibition of dynamin-mediated membrane fission by endophilin
- University of Geneva, Switzerland
- University of California, San Francisco, United States
- University of Utah, United States
- Howard Hughes Medical Institute, Yale University School of Medicine, United States
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.
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Author details
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.
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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Structural inhibition of dynamin-mediated membrane fission by endophilin
eLife 6:e26856.
https://doi.org/10.7554/eLife.26856
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