Molnar Cristina, de Celis Jose F
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
Mech Dev. 2006 May;123(5):337-51. doi: 10.1016/j.mod.2006.02.001. Epub 2006 May 8.
The three ERM proteins (Ezrin, Radixin and Moesin) form a conserved family required in many developmental processes involving regulation of the cytoskeleton. In general, the molecular function of ERM proteins is to link specific membrane proteins to the actin cytoskeleton. In Drosophila, loss of moesin (moe) activity causes incorrect localisation of maternal determinants during oogenesis, failures in rhabdomere differentiation in the eye and alterations of epithelial integrity in the wing imaginal disc. Some aspects of Drosophila Moe are related to the activity of the small GTPase RhoA, because the reduction of RhoA activity corrects many phenotypes of moe mutant embryos and imaginal discs. We have analysed the phenotype of moesin loss-of-function alleles in the wing disc and adult wing, and studied the effects of reduced Moesin activity on signalling mediated by the Notch, Decapentaplegic, Wingless and Hedgehog pathways. We found that reductions in Moesin levels in the wing disc cause the formation of wing-tissue vesicles and large thickenings of the vein L3, corresponding to breakdowns of epithelial continuity in the wing base and modifications of Hedgehog signalling in the wing blade, respectively. We did not observe any effect on signalling pathways other than Hedgehog, indicating that the moe defects in epithelial integrity have not generalised effects on cell signalling. The effects of moe mutants on Hedgehog signalling depend on the correct gene-dose of rhoA, suggesting that the requirements for Moesin in disc morphogenesis and Hh signalling in the wing disc are mediated by its regulation of RhoA activity. The mechanism linking Moesin activity with RhoA function and Hedgehog signalling remains to be elucidated.
三种ERM蛋白（埃兹蛋白、根蛋白和膜突蛋白）构成一个保守家族，在许多涉及细胞骨架调节的发育过程中发挥作用。一般来说，ERM蛋白的分子功能是将特定的膜蛋白与肌动蛋白细胞骨架相连。在果蝇中，膜突蛋白（moe）活性丧失会导致卵子发生过程中母体决定因子定位错误、眼睛中视杆细胞分化失败以及翅成虫盘上皮完整性改变。果蝇Moe的某些方面与小GTP酶RhoA的活性有关，因为RhoA活性降低可纠正moe突变胚胎和成虫盘的许多表型。我们分析了翅成虫盘和成虫翅膀中膜突蛋白功能缺失等位基因的表型，并研究了膜突蛋白活性降低对Notch、Decapentaplegic、Wingless和Hedgehog信号通路介导的信号传导的影响。我们发现，翅成虫盘中膜突蛋白水平降低会导致翅组织形成囊泡以及L3静脉大幅增厚，分别对应于翅基部上皮连续性的破坏和翅缘中Hedgehog信号传导的改变。除了Hedgehog信号通路外，我们未观察到对其他信号通路有任何影响，这表明moe在上皮完整性方面的缺陷并未对细胞信号传导产生普遍影响。moe突变体对Hedgehog信号传导的影响取决于rhoA的正确基因剂量，这表明翅成虫盘中盘形态发生和Hh信号传导中对膜突蛋白的需求是通过其对RhoA活性的调节来介导的。将膜突蛋白活性与RhoA功能及Hedgehog信号传导联系起来的机制仍有待阐明。
