Bearded family members inhibit neuralized-mediated endocytosis and signaling activity of Delta in Drosophila
Bearded family members inhibit neuralized-mediated endocytosis and signaling activity of Delta in Drosophila
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DOI：
10.1016/j.devcel.2005.12.017
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发表时间：
2006-02-01
影响因子：
11.8
通讯作者：
Schweisguth, F
中科院分区：
文献类型：
--
作者：
Bardin, AJ;Schweisguth, F
Notch受体配体在信号传导细胞中的内吞作用对于Notch受体活化是必不可少的。在果蝇中，E3泛素连接酶Neuralized（Neur）促进配体Delta（DI）的内吞作用和信号传导活性。在这项研究中，我们确定的胡子（Brd）家庭的蛋白质作为神经元的相互作用。我们表明，汤姆，一个原型的Brd家族成员，抑制神经依赖的Notch信号。Tom的过表达抑制DI的内吞作用并干扰DI与Neur的相互作用。Brd基因复合物的缺失导致DI在第5阶段胚胎的背侧细胞中的异位内吞。DI运输中的这种缺陷与专一基因的异位表达相关，专一基因是指定中外胚层的直接Notch靶基因。我们认为Brd蛋白对Neur的抑制对于DI信号的精确空间调节是重要的。
Endocytosis of Notch receptor ligands in signaling cells is essential for Notch receptor activation. In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (DI). In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. We show that Tom, a prototypic Brd family member, inhibits Neur-dependent Notch signaling. Overexpression of Tom inhibits the endocytosis of DI and interferes with the interaction of DI with Neur. Deletion of the Brd gene complex results in ectopic endocytosis of DI in dorsal cells of stage 5 embryos. This defect in DI trafficking is associated with ectopic expression of the single-minded gene, a direct Notch target gene that specifies the mesectoderm. We propose that inhibition of Neur by Brd proteins is important for precise spatial regulation of DI signaling.