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

David H. Gutmann, Larry Sherman, Liz Seftor, Carrie Haipek, Kimberly Hoang Lu, Mary Hendrix

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

The neurofibromatosis 2 (NF2) gene product, merlin, is a tumor suppressor protein mutated in schwannomas and several other tumors. Merlin, which shares significant homology with the actin-associated proteins ezrin, radixin and moesin (ERM proteins), inhibits cell growth when overexpressed in cell lines. The similarities between merlin and ERM proteins suggest that merlin's growth-regulatory capabilities may be due to alterations in cytoskeletal function. We examined this possibility in rat schwannoma cell lines overexpressing wild-type merlin isoforms and mutant merlin proteins. We found that overexpression of wild-type merlin resulted in transient alterations in F-actin organization, cell spreading and cell attachment. Merlin overexpression also impaired cell motility as measured in an in vitro motility assay. These effects were only observed in cells overexpressing a merlin isoform capable of inhibiting cell growth and not with mutant merlin molecules (NF2 patient mutations) or a merlin splice variant (isoform II) lacking growth-inhibitory activity. These data indicate that merlin may function to maintain normal cytoskeletal organization, and suggest that merlin's influence on cell growth depends on specific cytoskeletal rearrangements.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalHuman molecular genetics
Volume8
Issue number2
DOIs
StatePublished - Jan 1 1999

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