neurotic, a novel maternal neurogenic gene, encodes an O-fucosyltransferase that is essential for Notch-Delta interactions
neurotic, a novel maternal neurogenic gene, encodes an O-fucosyltransferase that is essential for Notch-Delta interactions
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DOI：
10.1242/dev.00679
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发表时间：
2003-10-01
期刊：
影响因子：
4.6
通讯作者：
Matsuno, K
中科院分区：
文献类型：
--
作者：
Sasamura, T;Sasaki, N;Matsuno, K
Notch信号在线虫和哺乳动物中高度保守，在许多发育过程中起着至关重要的作用。在果蝇胚胎中，Notch信号传导的缺陷导致神经增生，通常被称为神经原性表型。我们确定了一个新的母体神经基因，神经质，并表明它是必不可少的Notch信号。neurotic编码哺乳动物GDP-岩藻糖蛋白O-岩藻糖基转移酶的果蝇同源物，其将岩藻糖添加到表皮生长因子样重复序列，并且已知在Notch信号传导中起关键作用。神经症功能的细胞自主的方式，和遗传上位性测试表明，神经症是必需的全长，但不是激活形式的Notch的活动。此外，我们表明，神经质是必要的边缘活动，编码岩藻糖特异性β 1，3 N-乙酰葡糖胺转移酶，以前显示调节Notch受体活性。最后，神经质对于Notch与其配体Delta的物理相互作用以及Fringe在果蝇培养细胞中调节这种相互作用的能力是必不可少的。我们提出了一个前所未有的例子，一个蛋白质糖基化事件的配体-受体相互作用的绝对要求。我们的研究结果表明，O-岩藻糖基化催化的神经也参与了条纹的非依赖性活动的Notch，并可能提供一种新的开关机制，调节配体-受体相互作用。
Notch signalling, which is highly conserved from nematodes to mammals, plays crucial roles in many developmental processes. In the Drosophila embryo, deficiency in Notch signalling results in neural hyperplasia, commonly referred to as the neurogenic phenotype. We identify a novel maternal neurogenic gene, neurotic, and show that it is essential for Notch signalling. neurotic encodes a Drosophila homolog of mammalian GDP-fucose protein O-fucosyltransferase, which adds fucose sugar to epidermal growth factor-like repeats and is known to play a crucial role in Notch signalling. neurotic functions in a cell-autonomous manner, and genetic epistasis tests reveal that Neurotic is required for the activity of the full-length but not an activated form of Notch. Further, we show that neurotic is required for Fringe activity, which encodes a fucose-specific beta1,3 N-acetylglucosaminyltransferase, previously shown to modulate Notch receptor activity. Finally, Neurotic is essential for the physical interaction of Notch with its ligand Delta, and for the ability of Fringe to modulate this interaction in Drosophila cultured cells. We present an unprecedented example of an absolute requirement of a protein glycosylation event for a ligand-receptor interaction. Our results suggest that O-fucosylation catalysed by Neurotic is also involved in the Fringe-independent activities of Notch and may provide a novel on-off mechanism that regulates ligand-receptor interactions.