Fat facets and liquid facets promote Delta endocytosis and Delta signaling in the signaling cells
Fat facets and liquid facets promote Delta endocytosis and Delta signaling in the signaling cells
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DOI：
10.1242/dev.01434
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Fischer, JA
中科院分区：
文献类型：
--
作者：
Overstreet, E;Fitch, E;Fischer, JA
内吞作用调节信号细胞和接收细胞中的 Notch 信号通路。最近的一项假设是，信号细胞对配体 Delta 的内吞作用对于接收细胞中 Notch 的激活至关重要。在这里，我们提供有力支持该模型的证据。我们发现，在发育中的果蝇眼睛中，脂肪小面（Faf）（一种去泛素化酶）及其底物液体小面（Lqf）（一种内吞蛋白酶）促进信号细胞中的 Delta 内化和 Delta 信号传导。我们证明，虽然 Lqf 对于形态发生沟中三种不同的 Notch/Delta 信号传导事件是必需的，但 Faf 仅对于其中一种是必需的：光感受器前簇细胞的 Delta 信号传导，它可以防止异位神经元的募集。此外，我们还发现神经化泛素连接酶 (Neur) 能够泛素化 Delta，与 Faf 和 Lqf 一起在信号传导细胞中发挥作用。研究结果支持了一种神经功能模型，其中 Neur 通过刺激信号细胞中的 Delta 内化来增强 Delta 信号传导。我们认为 Faf 在 Delta 信号细胞中发挥着与 Neur 相似的作用。 Faf 通过去泛素化 Lqf 来增强 Delta 内化的效率，从而刺激 Delta 信号传导。
Endocytosis modulates the Notch signaling pathway in both the signaling and receiving cells. One recent hypothesis is that endocytosis of the ligand Delta by the signaling cells is essential for Notch activation in the receiving cells. Here, we present evidence in strong support of this model. We show that in the developing Drosophila eye Fat facets (Faf), a deubiquitinating enzyme, and its substrate Liquid facets (Lqf), an endocytic epsin, promote Delta internalization and Delta signaling in the signaling cells. We demonstrate that while Lqf is necessary for three different Notch/Delta signaling events at the morphogenetic furrow, Faf is essential only for one: Delta signaling by photoreceptor precluster cells, which prevents recruitment of ectopic neurons. In addition, we show that the ubiquitinligase Neuralized (Neur), which ubiquitinates Delta, functions in the signaling cells with Faf and Lqf. The results presented bolster one model for Neur function in which Neur enhances Delta signaling by stimulating Delta internalization in the signaling cells. We propose that Faf plays a role similar to that of Neur in the Delta signaling cells. By deubiquitinating Lqf, which enhances the efficiency of Delta internalization, Faf stimulates Delta signaling.