Ezrin enrichment on curved membranes requires a specific conformation or interaction with a curvature-sensitive partner
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
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.
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.
Metrics
-
- 3,758
- views
-
- 573
- downloads
-
- 58
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
- Physics of Living Systems
Recent experimental studies showed that electrically coupled neural networks like in mammalian inferior olive nucleus generate synchronized rhythmic activity by the subthreshold sinusoidal-like oscillations of the membrane voltage. Understanding the basic mechanism and its implication of such phenomena in the nervous system bears fundamental importance and requires preemptively the connectome information of a given nervous system. Inspired by these necessities of developing a theoretical and computational model to this end and, however, in the absence of connectome information for the inferior olive nucleus, here we investigated interference phenomena of the subthreshold oscillations in the reference system Caenorhabditis elegans for which the structural anatomical connectome was completely known recently. We evaluated how strongly the sinusoidal wave was transmitted between arbitrary two cells in the model network. The region of cell-pairs that are good at transmitting waves changed according to the wavenumber of the wave, for which we named a wavenumber-dependent transmission map. Also, we unraveled that (1) the transmission of all cell-pairs disappeared beyond a threshold wavenumber, (2) long distance and regular patterned transmission existed in the body-wall muscles part of the model network, and (3) major hub cell-pairs of the transmission were identified for many wavenumber conditions. A theoretical and computational model presented in this study provided fundamental insight for understanding how the multi-path constructive/destructive interference of the subthreshold oscillations propagating on electrically coupled neural networks could generate wavenumber-dependent synchronized rhythmic activity.
-
- Physics of Living Systems
The coordinated motion of animal groups through fluids is thought to reduce the cost of locomotion to individuals in the group. However, the connection between the spatial patterns observed in collectively moving animals and the energetic benefits at each position within the group remains unclear. To address this knowledge gap, we study the spontaneous emergence of cohesive formations in groups of fish, modeled as flapping foils, all heading in the same direction. We show in pairwise formations and with increasing group size that (1) in side-by-side arrangements, the reciprocal nature of flow coupling results in an equal distribution of energy requirements among all members, with reduction in cost of locomotion for swimmers flapping inphase but an increase in cost for swimmers flapping antiphase, and (2) in inline arrangements, flow coupling is non-reciprocal for all flapping phase, with energetic savings in favor of trailing swimmers, but only up to a finite number of swimmers, beyond which school cohesion and energetic benefits are lost at once. We explain these findings mechanistically and we provide efficient diagnostic tools for identifying locations in the wake of single and multiple swimmers that offer opportunities for hydrodynamic benefits to aspiring followers. Our results imply a connection between the resources generated by flow physics and social traits that influence greedy and cooperative group behavior.