边缘是一种修改Notch的糖系转移酶
D J Moloney1, V M Panin, S H Johnston
1Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, SUNY-Stony Brook, New York 11794-5215, USA.
Nature
|August 10, 2000
概括
边缘蛋白通过添加糖来修改Notch受体,这是细胞信号传递至关重要的过程. 这种糖基化机制影响细胞命运,对于理解细胞间通信至关重要.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 发展生物学 发展生物学
- 生物化学 生物化学
背景情况:
- 划分受体是细胞间信号通路的关键,调节细胞命运,增殖和亡.
- 边缘蛋白调节通过连接体的Notch受体激活.
- 边缘作用的精确生化机制仍然不清楚.
研究的目的:
- 阐明边缘蛋白调节Notch信号的生物化学机制.
- 为了研究Fringe介导的Notch受体的翻译后修饰的作用.
主要方法:
- 边缘蛋白活性的生物化学表征.
- 在体外酶测试以确定Fringe的基质特异性.
- 在哺乳动物细胞中进行共同培养测定,以评估Notch信号调制.
- 在Drosophila中表达酶上不活跃的边缘突变,以验证体内功能.
主要成果:
- 果虫和哺乳动物边缘蛋白质表现出糖特异的β1,3 N-乙烯基葡萄糖胺基转移酶活性.
- 边缘启动了O结合的糖残留在Notch受体的表皮生长因子样重复的延长.
- 生物测定证实了Fringe依赖的O-链接的Fucose延伸在Notch调节了Notch信号.
结论:
- 边缘蛋白质作为糖系转移酶起作用,通过O-链接的福克索延长来修改Notch受体.
- 这种翻译后的修改是调节Notch信号的关键机制.
- 边缘的差分受体糖基化代表了一种新的信号通路调制方式,与其他信号系统有潜在的相关性.
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