Abstract
Many signal transductions resulting from ligand–receptor interactions occur at the cell surface. These signaling pathways play essential roles in cell polarization, membrane morphogenesis, and the modulation of membrane tension at the cell surface. However, due to the large number of membrane-binding proteins, including actin-membrane linkers, and transmembrane proteins present at the cell surface, the molecular mechanisms underlying the regulation at the cell surface are yet unclear. Here, we describe the molecular functions of one of the key players at the cell surface, ezrin/radixin/moesin (ERM) proteins from a biophysical point of view. We focus our discussion on biophysical properties of ERM proteins revealed by using biophysical tools in live cells and in vitro reconstitution systems. We first describe the structural properties of ERM proteins and then discuss the interactions of ERM proteins with PI(4,5)P2 and the actin cytoskeleton. These properties of ERM proteins revealed by using biophysical approaches have led to a better understanding of their physiological functions in cells and tissues.
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Acknowledgements
We thank Prof. Pekka Lappalainen (HiLIFE - Institute of Biotechnology, University of Helsinki, Finland), Prof. Patricia Bassereau (Institut Curie, France), Prof. Emmanuel Lemichez (Institut Pasteur, France), and Prof. Ilpo Vattulainen (Department of Physics, University of Helsinki, Finland) for the insightful discussions.
Funding
This study was supported by the FY 2015 Researcher Exchange Program between the Japan Society for the Promotion of Science (JSPS) and Academy of Finland (AF), Astellas Foundation for Research on Metabolic Disorders, Scandinavia-Japan Sasakawa Foundation, Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, The Association for Fordays Self-Reliance Support in Japan, Okayama Foundation for Science and Technology, ONO Medical Research Foundation, Takeda Science Foundation, The Naito Foundation, The Company of Biologists, European Biophysical Societies Association (EBSA), and Institut Curie, Centre National de la Recherche Scientifique (CNRS).
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Yosuke Senju and Feng-Ching Tsai had the idea for the article. Yosuke Senju and Feng-Ching Tsai performed the literature search. Yosuke Senju and Feng-Ching Tsai drafted and critically revised the work.
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Fig. S1 (EPS 1805 kb)
(a) A simple phylogenetic tree of ERM proteins.
(b) The microarray gene expression profiles of Homo sapiens ERM proteins in various cell lines and tissues generated by BioGPS. Note that the expression levels of ezrin/radoxin/moesin are different in cell lines and tissues.
(c) Protein-protein interaction (PPI) network analysis. Some known and predicted PPIs of ERM proteins are analyzed using stringApp in Cytoscape.
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Senju, Y., Tsai, FC. A biophysical perspective of the regulatory mechanisms of ezrin/radixin/moesin proteins. Biophys Rev 14, 199–208 (2022). https://doi.org/10.1007/s12551-021-00928-0
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DOI: https://doi.org/10.1007/s12551-021-00928-0