The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association

The neurofibromatosis 2 protein product merlin, named for its relatedness t o the ezrin, radixin and moesin (ERM) family of proteins, is a tumour suppr essor whose absence results in the occurrence of multiple tumours of the ne rvous system, particularly schwannomas and meningiomas. Merlin's similarity to ERMs suggests that it might share functions, acting as a link between c ytoskeletal components and the cell membrane. The N-terminus of merlin has strong sequence identity to the N-terminal actin-binding region of ezrin; h ere we describe in detail the merlin-actin interaction. Employing standard actin co-sedimentation assays, we have determined that merlin isoform 2 bin ds F-actin with an apparent binding constant of 3.6 muM and a stoichiometry of 1 mol of merlin per 11.5 mol of actin in filaments at saturation. Furth er, solid-phase binding assays reveal that merlin isoforms 1 and 2 bind act in filaments differentially, suggesting that the intramolecular interaction s in isoform 1 might hinder its ability to bind actin. However, merlin does not bind G-actin. Studies of actin filament dynamics show that merlin slow s filament disassembly with no influence on the assembly rate, indicating t hat merlin binds along actin filament lengths. This conclusion is supported by electron microscopy, which demonstrates that merlin binds periodically along cytoskeletal actin filaments. Comparison of these findings with those reported for ERM proteins reveal a distinct role for merlin in actin filam ent dynamics.