Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesion and spreading
Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesion and spreading
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DOI：
10.1093/hmg/8.2.267
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发表时间：
1999-02-01
影响因子：
3.5
通讯作者：
Hendrix, M
中科院分区：
文献类型：
--
作者：
Gutmann, DH;Sherman, L;Hendrix, M
神经纤维瘤病2（NF 2）基因产物Merlin是一种在神经鞘瘤和其他几种肿瘤中突变的肿瘤抑制蛋白。Merlin与肌动蛋白相关蛋白ezrin、radixin和moesin（ERM蛋白）具有显著的同源性，当在细胞系中过表达时，Merlin抑制细胞生长。Merlin和ERM蛋白之间的相似性表明，Merlin的生长调节能力可能是由于细胞骨架功能的改变。我们在过表达野生型梅林蛋白亚型和突变型梅林蛋白的大鼠神经鞘瘤细胞系中研究了这种可能性。我们发现，野生型merlin的过度表达导致F-肌动蛋白组织，细胞铺展和细胞附着的短暂改变，Merlin过度表达也损害了细胞运动性，如在体外运动性测定中所测量的。这些作用仅在过度表达能够抑制细胞生长的merlin亚型的细胞中观察到，而在突变的merlin分子（NF 2患者突变）或缺乏生长抑制活性的merlin剪接变体（亚型II）中未观察到。这些数据表明，merlin可能起维持正常细胞骨架组织的作用，并表明merlin对细胞生长的影响取决于特定的细胞骨架重排。
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.