Xu H M, Gutmann D H
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci Res. 1998 Feb 1;51(3):403-15. doi: 10.1002/(SICI)1097-4547(19980201)51:3<403::AID-JNR13>3.0.CO;2-7.
The neurofibromatosis 2 (NF2) suppressor gene encodes a protein termed merlin (or schwannomin) with sequence similarity to a family of proteins that link the actin cytoskeleton to cell surface glycoproteins. Members of this ERM family of proteins include ezrin, radixin, and moesin. These proteins contain a carboxyl (C-) terminus actin binding site. In contrast to the ERM proteins, merlin lacks the conventional C-terminal actin binding site, but still localizes to the ruffling edge of plasma membranes. In this study, we investigate the ability of merlin to interact with actin through a nonconventional actin binding domain. We demonstrate for the first time that merlin can associate with polymerized actin in vitro by virtue of an amino (N-) terminal actin binding domain including residues 178-367. Merlin actin binding is not affected by several naturally-occurring NF2 patient mutations or alternatively spliced isoforms. These results suggest that merlin, like other ERM proteins, can directly interact with the actin cytoskeleton. In addition, merlin associates with polymerized microtubules in vitro using a novel microtubule binding region in the N-terminal region of merlin that is masked in the full-length merlin molecule, such that wild-type functional merlin in the "closed" conformation fails to bind polymerized microtubules. These microtubule association results confirm the notion that merlin exists in "open" and "closed" conformations relevant to its function as a negative growth regulator.
神经纤维瘤病2型（NF2）抑癌基因编码一种名为默林（或施万宁）的蛋白质，该蛋白质与一类将肌动蛋白细胞骨架与细胞表面糖蛋白相连的蛋白质家族具有序列相似性。这个ERM蛋白质家族的成员包括埃兹蛋白、根蛋白和膜突蛋白。这些蛋白质含有一个羧基（C-）末端肌动蛋白结合位点。与ERM蛋白质不同，默林缺乏传统的C末端肌动蛋白结合位点，但仍定位于质膜的边缘褶皱处。在本研究中，我们研究了默林通过一个非常规肌动蛋白结合域与肌动蛋白相互作用的能力。我们首次证明，默林可凭借一个包括第178至367位残基的氨基（N-）末端肌动蛋白结合域在体外与聚合肌动蛋白结合。默林与肌动蛋白的结合不受几种自然发生的NF2患者突变或可变剪接异构体的影响。这些结果表明，默林与其他ERM蛋白质一样，可直接与肌动蛋白细胞骨架相互作用。此外，默林利用默林N末端区域中一个新的微管结合区域在体外与聚合微管结合，该区域在全长默林分子中被掩盖，使得处于“封闭”构象的野生型功能性默林无法结合聚合微管。这些微管结合结果证实了这样一种观点，即默林以与其作为负生长调节因子功能相关的“开放”和“封闭”构象存在。
