An MBoC Favorite: Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site

Abstract

The ezrin, radixin, and moesin (ERM) proteins have emerged as important regulators of the cortical actin cytoskeleton, particularly in the apical domain of polarized epithelial cells. In this paper (Gary and Bretscher, 1995), which has been cited more than 250 times since publication, the authors showed that head-to-tail binding regulates interactions with actin and other binding partners at the cell cortex. Intramolecular head-to-tail binding has subsequently been shown to be critical for regulation of ERM proteins, as well as for the closely related protein Merlin, a component of the Hippo growth control pathway. ERM folding has also served as a model for autoinhibition of a number of other cortical cytoskeletal proteins. Interestingly, although the authors’ data suggested the existence of both intramolecular and intermolecular interactions, little is known about the importance of the latter in living cells, suggesting that the full importance of this work remains to be discovered.