Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesionand spreading |
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Authors: | Gutmann DH; Sherman L; Seftor L; Haipek C; Hoang Lu K; Hendrix M |
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Institution: | The Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA. gutmannd@neuro.wustl.edu |
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Abstract: | The neurofibromatosis 2 ( NF2 ) gene product, merlin, is a tumor suppressor
protein mutated in schwanno-mas 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.
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