Pitsouli Chrysoula, Delidakis Christos
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion, Greece.
Development. 2005 Sep;132(18):4041-50. doi: 10.1242/dev.01979. Epub 2005 Aug 10.
Lateral inhibition is a pattern refining process that generates single neural precursors from a field of equipotent cells and is mediated via Notch signaling. Of the two Notch ligands Delta and Serrate, only the former was thought to participate in this process. We now show that macrochaete lateral inhibition involves both Delta and Serrate. In this context, Serrate interacts with Neuralized, a ubiquitin ligase that was heretofore thought to act only on Delta. Neuralized physically associates with Serrate and stimulates its endocytosis and signaling activity. We also characterize a mutation in mib1, a Drosophila homolog of mind bomb, another Delta-targeting ubiquitin ligase from zebrafish. Mib1 affects the signaling activity of Delta and Serrate in both lateral inhibition and wing dorsoventral boundary formation. Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling.
侧向抑制是一种模式细化过程，它从一群等效细胞中产生单个神经前体，并通过Notch信号传导介导。在两种Notch配体Delta和锯齿蛋白中，以前认为只有前者参与这一过程。我们现在表明，刚毛侧向抑制涉及Delta和锯齿蛋白。在这种情况下，锯齿蛋白与神经化蛋白相互作用，神经化蛋白是一种泛素连接酶，此前认为它仅作用于Delta。神经化蛋白与锯齿蛋白发生物理结合，并刺激其胞吞作用和信号活性。我们还鉴定了mib1的一个突变，mib1是mind bomb的果蝇同源物，mind bomb是来自斑马鱼的另一种靶向Delta的泛素连接酶。Mib1在侧向抑制和翅背腹边界形成中均影响Delta和锯齿蛋白的信号活性。在上述两种情况下，同时缺失神经化蛋白和mib1会完全消除Notch信号传导，这表明泛素化可能是Delta/锯齿蛋白信号传导的一个先决条件。
