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Structural inhibition of dynamin-mediated membrane fission by endophilin

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...

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Autores principales: Hohendahl, Annika, Talledge, Nathaniel, Galli, Valentina, Shen, Peter S, Humbert, Frédéric, De Camilli, Pietro, Frost, Adam, Roux, Aurélien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663480/
https://www.ncbi.nlm.nih.gov/pubmed/28933693
http://dx.doi.org/10.7554/eLife.26856
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author Hohendahl, Annika
Talledge, Nathaniel
Galli, Valentina
Shen, Peter S
Humbert, Frédéric
De Camilli, Pietro
Frost, Adam
Roux, Aurélien
author_facet Hohendahl, Annika
Talledge, Nathaniel
Galli, Valentina
Shen, Peter S
Humbert, Frédéric
De Camilli, Pietro
Frost, Adam
Roux, Aurélien
author_sort Hohendahl, Annika
collection PubMed
description 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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spelling pubmed-56634802017-11-01 Structural inhibition of dynamin-mediated membrane fission by endophilin Hohendahl, Annika Talledge, Nathaniel Galli, Valentina Shen, Peter S Humbert, Frédéric De Camilli, Pietro Frost, Adam Roux, Aurélien eLife Structural Biology and Molecular Biophysics 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. eLife Sciences Publications, Ltd 2017-09-21 /pmc/articles/PMC5663480/ /pubmed/28933693 http://dx.doi.org/10.7554/eLife.26856 Text en © 2017, Hohendahl et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Structural Biology and Molecular Biophysics
Hohendahl, Annika
Talledge, Nathaniel
Galli, Valentina
Shen, Peter S
Humbert, Frédéric
De Camilli, Pietro
Frost, Adam
Roux, Aurélien
Structural inhibition of dynamin-mediated membrane fission by endophilin
title Structural inhibition of dynamin-mediated membrane fission by endophilin
title_full Structural inhibition of dynamin-mediated membrane fission by endophilin
title_fullStr Structural inhibition of dynamin-mediated membrane fission by endophilin
title_full_unstemmed Structural inhibition of dynamin-mediated membrane fission by endophilin
title_short Structural inhibition of dynamin-mediated membrane fission by endophilin
title_sort structural inhibition of dynamin-mediated membrane fission by endophilin
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663480/
https://www.ncbi.nlm.nih.gov/pubmed/28933693
http://dx.doi.org/10.7554/eLife.26856
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