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Elife. 2017 Sep 21;6. pii: e26856. doi: 10.7554/eLife.26856.

Structural inhibition of dynamin-mediated membrane fission by endophilin.

Hohendahl A#1, Talledge N#2,3,4,5, Galli V1, Shen PS4, Humbert F1, De Camilli P6,7,8,9,10, Frost A2,3,4,5, Roux A1,11.

Author information

1
Biochemistry Department, University of Geneva, Geneva, Switzerland.
2
Department of Biochemistry and Biophysics, University of California, San Francisco, United States.
3
California Institute for Quantitative Biomedical Research, University of California, San Francisco, United States.
4
Department of Biochemistry, University of Utah, Salt Lake City, United States.
5
Chan Zuckerberg Biohub, San Francisco, United States.
6
Department of Neuroscience, Yale University School of Medicine, New Haven, United States.
7
Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States.
8
Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, United States.
9
Department of Cell Biology, Yale University School of Medicine, New Haven, United States.
10
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
11
Swiss National Centre for Competence in Research Programme Chemical Biology, Geneva, Switzerland.
#
Contributed equally

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.

KEYWORDS:

BAR domain; biophysics; cell biology; dynamin; endocytosis; endophilin; membrane fission; none; structural biology

PMID:
28933693
PMCID:
PMC5663480
DOI:
10.7554/eLife.26856
[Indexed for MEDLINE]
Free PMC Article

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