Slik and the Receptor Tyrosine Kinase Breathless Mediate Localized Activation of Moesin in Terminal Tracheal Cells

A key element in the regulation of subcellular branching and tube morphogenesis of the Drosophila tracheal system is the organization of the actin cytoskeleton by the ERM protein Moesin. Activation of Moesin within specific subdomains of cells, critical for its interaction with actin, is a tightly controlled process and involves regulatory inputs from membrane proteins, kinases and phosphatases. The kinases that activate Moesin in tracheal cells are not known. Here we show that the Sterile-20 like kinase Slik, enriched at the luminal membrane, is necessary for the activation of Moesin at the luminal membrane and regulates branching and subcellular tube morphogenesis of terminal cells. Our results reveal the FGF-receptor Breathless as an additional necessary cue for the activation of Moesin in terminal cells. Breathless-mediated activation of Moesin is independent of the canonical MAP kinase pathway.

调控果蝇气管系统细胞内分支与管状形态发生的关键环节，是ERM蛋白Moesin对肌动蛋白细胞骨架（actin cytoskeleton）的组织作用。Moesin在细胞特定亚结构域内的激活是其与肌动蛋白结合的关键，该过程受严格调控，依赖膜蛋白、激酶及磷酸酶提供的调控信号输入。目前尚不明确在气管细胞中激活Moesin的激酶类型。本研究发现，富集于管腔膜的类Ste20激酶Slik是管腔膜Moesin激活所必需的因子，同时可调控气管末端细胞的细胞内分支与管状形态发生。本研究结果同时表明，成纤维细胞生长因子受体（FGF-receptor）Breathless是调控气管末端细胞Moesin激活的另一必要信号。Breathless介导的Moesin激活过程不依赖于经典MAP激酶通路。