ERM proteins

compensate for one another, although there is no evidence of true biochemical redundancy. The genomes of lower organisms, such as Caenorhabditis elegans, Drosophila melanogaster and Danio rerio, harbor single ERM orthologues; in fact, ERMs appeared evolutionarily during the transition to multicellularity and an ERM-like protein is encoded by the genome of the choanoflagellate Monosiga brevicolis, which is thought to be the closest metazoan ancestor. Interestingly, within the FERM protein superfamily tree the ERMs form a tightly related branch that includes one other family member and its orthologues: the neurofibromatosis type 2 tumor suppressor protein, merlin (moesin, ezrin, radixin like protein). The structure of the ERM proteins is integral to what they do. They have an amino-terminal clover-leaf-shaped FERM domain that harbors many protein interacting sites. This domain is connected to a carboxy-terminal actinbinding domain via a central a-helix-rich segment. The carboxy-terminal and a-helical domains can both fold back upon the FERM domain and mask both actin-binding and FERMdomain interactions. Regulation of this conformation by phosphorylation and phospholipid binding modulates ERM activity. In this way, the ERMs can assemble protein complexes at the membrane and link them to the actin cytoskeleton in a regulated fashion. The ERMs therefore seem designed to do several things, perhaps all at once: alter the mechanical properties of the ERM proteins