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.

果蝇气管系统的亚细胞分支与管状形态发生调控过程中的核心调控因素，是由ERM蛋白Moesin（ERM protein Moesin）介导的肌动蛋白细胞骨架组织。Moesin在细胞特定亚结构域内的激活——这对其与肌动蛋白的相互作用至关重要——是一项受到严格调控的过程，该过程涉及膜蛋白、激酶与磷酸酶提供的调控输入信号。目前尚未明确在气管细胞中激活Moesin的激酶种类。本研究发现，富集于管腔膜的STE20样激酶Slik（Sterile-20 like kinase Slik）是管腔膜处Moesin激活的必需条件，并可调控终末细胞的分支进程与亚细胞管状形态发生。本研究结果揭示，成纤维细胞生长因子受体Breathless（FGF-receptor Breathless）是调控终末细胞内Moesin激活的另一必需信号。Breathless介导的Moesin激活过程不依赖于经典的丝裂原活化蛋白激酶（MAPK）通路。