Université de Toulouse UPS, Centre de Biologie du Développement, Toulouse, France.
J Cell Sci. 2010 Jun 15;123(Pt 12):2058-67. doi: 10.1242/jcs.064550.
The ezrin, radixin and moesin (ERM) proteins regulate cell membrane architecture in several cellular contexts. Current models propose that ERM activation requires a PtdIns(4,5)P(2)-induced conformational change, followed by phosphorylation of a conserved threonine. However, how these inputs contribute in vivo to orchestrate ERM activation is poorly understood. We addressed this issue by evaluating the contribution of PtdIns(4,5)P(2) and phosphorylation to the regulation of moesin during Drosophila development. Unexpectedly, we found that a form of moesin that cannot be phosphorylated displayed significant activity and could substitute for the endogenous product during wing morphogenesis. By contrast, we also show that PtdIns(4,5)P(2) binding is essential for moesin recruitment to the membrane and for its subsequent phosphorylation. Our data indicate that PtdIns(4,5)P(2) acts as a dosing mechanism that locally regulates ERM membrane recruitment and activation, whereas cycles of phosphorylation and dephosphorylation further control their activity once they have reached the cell cortex.
埃兹蛋白、根蛋白和膜突蛋白（ERM）家族在多种细胞环境中调节细胞膜结构。目前的模型提出，ERM 的激活需要 PtdIns（4,5）P2 诱导的构象变化，然后是保守苏氨酸的磷酸化。然而，这些输入在体内如何协调 ERM 的激活还知之甚少。我们通过评估 PtdIns（4,5）P2 和磷酸化在果蝇发育过程中对膜突蛋白调节的贡献来解决这个问题。出乎意料的是，我们发现一种不能被磷酸化的膜突蛋白形式表现出显著的活性，并在翅膀形态发生过程中可以替代内源性产物。相比之下，我们还表明 PtdIns（4,5）P2 结合对于膜突蛋白向膜的募集及其随后的磷酸化是必不可少的。我们的数据表明，PtdIns（4,5）P2 作为一种剂量机制，局部调节 ERM 膜的募集和激活，而磷酸化和去磷酸化的循环进一步控制它们一旦到达细胞皮质的活性。
