Department of Medical Genetics, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
J Cell Sci. 2010 Apr 1;123(Pt 7):1099-107. doi: 10.1242/jcs.059469. Epub 2010 Mar 9.
Organization of the plasma membrane in polarized epithelial cells is accomplished by the specific localization of transmembrane or membrane-associated proteins, which are often linked to cytoplasmic protein complexes, including the actin cytoskeleton. In this study, we identified Sip1 as a Drosophila orthologue of the ezrin-radixin-moesin (ERM) binding protein 50 (EBP50; also known as the Na(+)/H(+) exchanger regulatory factor NHERF1). In mammals, EBP50/NHERF1 is a scaffold protein required for the regulation of several transmembrane receptors and downstream signal transduction activity. In Drosophila, loss of Sip1 leads to a reduction in Slik kinase protein abundance, loss of Moesin phosphorylation and changes in epithelial structure, including mislocalization of E-cadherin and F-actin. Consistent with these findings, Moesin and Sip1 act synergistically in genetic-interaction experiments, and Sip1 protein abundance is dependent on Moesin. Co-immunoprecipitation experiments indicate that Sip1 forms a complex with both Moesin and Slik. Taken together, these data suggest that Sip1 promotes Slik-dependent phosphorylation of Moesin, and suggests a mechanism for the regulation of Moesin activity within the cell to maintain epithelial integrity.
在极化上皮细胞中，质膜的组织是通过跨膜或膜相关蛋白的特异性定位来完成的，这些蛋白通常与细胞质蛋白复合物相连，包括肌动蛋白细胞骨架。在这项研究中，我们鉴定出 Sip1 是果蝇 ezrin-radixin-moesin (ERM) 结合蛋白 50 (EBP50; 也称为 Na(+)/H(+) 交换体调节因子 NHERF1)的同源物。在哺乳动物中，EBP50/NHERF1 是一种支架蛋白，是调节几种跨膜受体和下游信号转导活性所必需的。在果蝇中，Sip1 的缺失导致 Slik 激酶蛋白丰度降低、Moesin 磷酸化丧失以及上皮结构改变，包括 E-钙粘蛋白和 F-肌动蛋白的定位错误。与这些发现一致的是，Moesin 和 Sip1 在遗传相互作用实验中协同作用，并且 Sip1 蛋白丰度依赖于 Moesin。共免疫沉淀实验表明，Sip1 与 Moesin 和 Slik 都形成复合物。总之，这些数据表明 Sip1 促进了 Moesin 依赖于 Slik 的磷酸化，并提出了一种在细胞内调节 Moesin 活性以维持上皮完整性的机制。
