ERM-merlin and EBP50 protein families in plasma membrane organization and function

The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regul atory molecules in linking F-actin to specific membrane proteins, especiall y in cell surface structures. Merlin, the product of the NF2 tumor suppress or gene, has sequence similarity to ERM proteins and binds to some of the s ame membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Acti vation of at least ERM proteins can be accomplished by C-terminal phosphory lation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function o f these proteins in cortical structure, endocytic traffic, signal transduct ion, and growth control is discussed.