moesin

Moesin is a cytoskeletal linker protein belonging to the ezrin–radixin–moesin (ERM) family. It is encoded by the MSN gene and is widely expressed in many tissues, with prominent localization at the inner surface of the plasma membrane. Moesin functions to connect membrane proteins to the actin cytoskeleton, contributing to the organization of cell surface structures such as microvilli and to the maintenance of cell shape and polarity.

Structurally, moesin contains an N-terminal FERM domain that interacts with membrane proteins and phosphoinositides, a central helical domain, and a C-terminal actin-binding domain. In its resting state, moesin adopts a closed conformation through an intramolecular interaction between the N- and C-terminal regions, which prevents simultaneous binding to membrane partners and actin. Activation involves disruption of this autoinhibition, driven by binding of phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphorylation at a conserved C-terminal threonine residue (T558 in humans). Kinases such as lymphocyte-oriented kinase (LOK/STK10) mediate this phosphorylation in certain cell types, enabling moesin to link membrane proteins (for example, CD44) to the actin cytoskeleton.

Functions and roles of moesin include regulation of cell shape, adhesion, motility, and cortical stability. It participates in the formation and maintenance of microvilli, contributes to signal transduction at the plasma membrane, and plays a role in immune cell activation and migration. Moesin also participates in intracellular polarity and vesicular trafficking in various cell contexts.

Moesin interacts with multiple membrane partners and the actin cytoskeleton, and its activity is modulated by phosphorylation and lipid binding. Altered expression or phosphorylation of ERM proteins, including moesin, has been observed in several physiological and pathological settings, reflecting its role in dynamic membrane–cytoskeleton organization.