Ezrin enrichment on curved membranes requires a specific conformation or interaction with a curvature-sensitive partner
- Institut Curie, France
- University of Helsinki, Finland
- Université Côte d'Azur, France
- Institut de Recherche en Infectiologie de Montpellier (IRIM), France
- Institut Pasteur, France
Abstract
One challenge in cell biology is to decipher the biophysical mechanisms governing protein enrichment on curved membranes and the resulting membrane deformation. The ERM protein ezrin is abundant and associated with cellular membranes that are flat, positively or negatively curved. Using in vitro and cell biology approaches, we assess mechanisms of ezrin's enrichment on curved membranes. We evidence that wild-type ezrin (ezrinWT) and its phosphomimetic mutant T567D (ezrinTD) do not deform membranes but self-assemble anti-parallelly, zipping adjacent membranes. EzrinTD's specific conformation reduces intermolecular interactions, allows binding to actin filaments, which reduces membrane tethering, and promotes ezrin binding to positively-curved membranes. While neither ezrinTD nor ezrinWT senses negative curvature alone, we demonstrate that interacting with curvature-sensing I-BAR-domain proteins facilitates ezrin enrichment in negatively-curved membrane protrusions. Overall, our work demonstrates that ezrin can tether membranes, or be targeted to curved membranes, depending on conformations and interactions with actin and curvature-sensing binding partners.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for the following figuresFigure 1 - figure supplement 1C, 1D, and 1GFigure 4 - figure supplement 1A and 1B.
Article and author information
Author details
Patricia Bassereau
Funding
Agence Nationale de la Recherche (ANR-15-CE18-0016-03)
- Meng-Chen Tsai
- Emmanuel Lemichez
- Patricia Bassereau
H2020 European Research Council (339847)
- Stephanie Miserey-Lenkei
- Evelyne Coudrier
- Patricia Bassereau
Human Frontier Science Program (RGP0005/2016)
- Yosuke Senju
- Pekka Lappalainen
- Evelyne Coudrier
- Patricia Bassereau
European Molecular Biology Organization (ALTF 1527-2014)
- Feng-Ching Tsai
H2020 Marie Skłodowska-Curie Actions (H2020-MSCA-IF-2014)
- Feng-Ching Tsai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anna Akhmanova, Utrecht University, Netherlands
Version history
- Received: April 4, 2018
- Accepted: September 14, 2018
- Accepted Manuscript published: September 20, 2018 (version 1)
- Version of Record published: October 1, 2018 (version 2)
Copyright
© 2018, Tsai 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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Ezrin enrichment on curved membranes requires a specific conformation or interaction with a curvature-sensitive partner
eLife 7:e37262.
https://doi.org/10.7554/eLife.37262
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