Epithelial cells (green) go for a walk when Moesin is missing (right).


Epithelial cells are ready to run off at any moment, at least based on the results of Olga Speck, Richard Fehon (Duke University, Durham, NC), and colleagues. They have found that moesin, previously thought to be a stolid structural component, is actually a signaling protein that maintains epithelial cell identity by suppressing Rho activity.

Ezrin, radixin, and moesin (ERM)—represented only by Moesin in flies—are proteins that link actin to various transmembrane proteins at the apical surface of epithelial cells. The link was thought to help maintain epithelial structures such as microvilli, but Fehon's group found that flies lacking Moesin had epithelial cells that lost polarity, dropped out of monolayers, and migrated invasively.

Moesin appears to act by suppressing Rho. Interfering with ERM proteins in mammalian epithelial cells boosted Rho activity, and fly Moesin mutants improved when Rho1 dose was halved. Rho1 overexpression in wild type, however, phenocopied Moesin loss.Thus epithelial cells must be actively maintained in their polarized state, lest they slip off into the motile night. This instability may reflect the transitions from structured epithelium to motile founder cells that occur frequently during development—a transition that carcinoma cells apparently recapitulate when they become metastatic. ▪


Speck, O., et al.