Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesion and spreading

The neurofibromatosis 2 (NF2) gene product, merlin, is a tumor suppressor p rotein mutated in schwannomas and several other tumors. Merlin, which share s significant homology with the actin-associated proteins ezrin, radixin an d moesin (ERM proteins), inhibits cell growth when overexpressed in cell li nes, The similarities between merlin and ERM proteins suggest that merlin's growth-regulatory capabilities may be due to alterations in cytoskeletal f unction. We examined this possibility in rat schwannoma cell lines overexpr essing wild-type merlin isoforms and mutant merlin proteins. We found that overexpression of wild-type merlin resulted in transient alterations in F-a ctin organization, cell spreading and cell attachment, Merlin overexpressio n also impaired cell motility as measured in an in vitro motility assay. Th ese effects were only observed in cells overexpressing a merlin isoform cap able of inhibiting cell growth and not with mutant merlin molecules (NF2 pa tient mutations) or a merlin splice variant (isoform II) lacking growth-inh ibitory activity, These data indicate that merlin may function to maintain normal cytoskeletal organization, and suggest that merlin's influence on ce ll growth depends on specific cytoskeletal rearrangements.