ezrinradixinmoesin

Ezrin-radixin-moesin (ERM) proteins are a family of cytoskeletal linker proteins that connect the plasma membrane to the actin cytoskeleton. The three vertebrate members are ezrin, radixin, and moesin, encoded by the EZR, RDX, and MSN genes respectively. ERM proteins are broadly expressed and play key roles in shaping the cell surface, membrane–cytoskeleton organization, and signal transduction.

Structurally, ERM proteins possess an N-terminal FERM domain that binds the cytoplasmic tails of transmembrane proteins, a central helical region, and a C-terminal actin-binding site. In their resting state, ERM proteins adopt a closed, auto-inhibited conformation due to intramolecular interactions between the N- and C-terminal ends. Activation involves two main events: binding to phosphatidylinositol 4,5-bisphosphate (PIP2) at the membrane and phosphorylation of a conserved threonine residue in the C-terminal regulatory domain (T567 in ezrin, T564 in radixin, T558 in moesin). These changes release autoinhibition and permit concurrent engagement with membrane proteins and F-actin.

Functionally, ERM proteins serve as adapters linking membrane proteins such as CD44 and other receptors to the actin cytoskeleton, contributing to the formation of microvilli, maintenance of cell shape and polarity, and regulation of cell adhesion and migration. They also participate in endocytosis and signal transduction at the plasma membrane, with regulation by kinases and lipid signaling pathways.

Genetically, the ERM family is evolutionarily conserved across metazoans and belongs to the band 4.1 superfamily. Dysregulation of ERM activity has been connected to developmental abnormalities and cancer progression, reflecting their essential role in dynamic cell surfaces.