A glimpse of the ERM proteins.

Godwin A Ponuwei

doi:10.1186/s12929-016-0246-3

Abstract

In all eukaryotes, the plasma membrane is critically important as it maintains the architectural integrity of the cell. Proper anchorage and interaction between the plasma membrane and the cytoskeleton is critical for normal cellular processes. The ERM (ezrin-radixin-moesin) proteins are a class of highly homologous proteins involved in linking the plasma membrane to the cortical actin cytoskeleton. This review takes a succinct look at the biology of the ERM proteins including their structure and function. Current reports on their regulation that leads to activation and deactivation was examined before taking a look at the different interacting partners. Finally, emerging roles of each of the ERM family members in cancer was highlighted.

Highlights

Structure of ERM proteins Structurally, at the amino terminus of ERM proteins is an approximately 1-296 amino acid Four point one ERM domain (FERM) domain known as N-terminal ERM association domain (NERMAD) through which they interact with cell membranes
Recruitment of ERMs to areas of the plasma membrane containing high amount of phosphoinositides such as Phosphatidylinositol 4 (PIP2) exposes a conserved regulatory threonine phosphorylation residue (T567, T564 and T558 in ezrin, radixin and moesin respectively) located in the C-ERMAD domain [14], and this induces a successive activation mechanism whereby PIP2 first bind to a subdomain in the N-terminal FERM domain followed by plasma membrane translocation and phosphorylation of the threonine residues [15]
Phosphorylation of the conserved threonine residue can be induced by different signaling protein kinases such as Rho-associated protein kinase (ROCK), myotonic dystrophy kinase-related Cdc42-binding kinase, G-protein coupled receptor kinase 2, Nck interacting kinase [14, 18,19,20], protein kinase C (PKCα, PKCβ), NFкB-inducing kinase (NIK), lymphocyte-oriented kinase (LOK) thereby creating stearic hindrance that keeps the FERM and C-ERMAD domains apart [11, 21,22,23], and this stabilizes the active state of ERM proteins in their open conformation [15, 17]

Summary

Introduction

Structure of ERM proteins Structurally, at the amino terminus of ERM proteins is an approximately 1-296 amino acid FERM domain known as N-terminal ERM association domain (NERMAD) through which they interact with cell membranes. Recruitment of ERMs to areas of the plasma membrane containing high amount of phosphoinositides such as PIP2 exposes a conserved regulatory threonine phosphorylation residue (T567, T564 and T558 in ezrin, radixin and moesin respectively) located in the C-ERMAD domain [14], and this induces a successive activation mechanism whereby PIP2 first bind to a subdomain in the N-terminal FERM domain followed by plasma membrane translocation and phosphorylation of the threonine residues [15].

Results

Conclusion