在缺少POFUT1的小鼠肠道细胞中,EOGT可启用剩余的Notch信号
Mohd Nauman1, Shweta Varshney1,2, Jiahn Choi1
1Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., New York, NY, 10641, USA.
Scientific reports
|October 14, 2023
概括
蛋白质O-fucosyltransferase1 (Pofut1) 和EGF特定的O-链接N-乙糖胺转移酶 (Eogt) 对于小鼠肠道中的Notch信号至关重要. 无论是O-fucose还是O-GlcNAc甘氨酸都支持肠道发育和生存.
科学领域:
- 发育生物学 发展生物学
- 葡萄糖生物学 葡萄糖生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 痕信号对于小鼠肠道中细胞命运的确定至关重要.
- 诺奇受体上的O-甘氨酸调节信号传递,其中蛋白质O-fucosyltransferase 1 (Pofut1) 起着关键作用.
- 在肠道中有条件的Pofut1删除减少了Notch信号,但允许生存,而不是完全消除Notch通路.
研究的目的:
- 调查EGF特定的O链N-乙糖胺转移酶 (Eogt) 在补偿肠道Notch信号中的Pofut1损失方面的作用.
- 为了确定Eogt介导的剩余Notch信号是否支持肠道中缺乏Pofut1的小鼠的生存.
主要方法:
- 在小鼠肠道中删除Pofut1和Eogt的条件基因.
- 对肠道发育,细胞系组成 (杯子,帕内斯细胞) 和诺奇标基因表达 (Hes1) 的分析.
- 对转基因小鼠的体重和生存率的评估.
主要成果:
- 仅全球Eogt删除本身并没有显著影响肠道发育.
- 与POFUT1缺乏的小鼠相比,缺乏POFUT1和EOGT的小鼠的生存率降低,体重减轻较大,玻璃杯和帕内斯细胞增加,Hes1的下调.
- 剩余的Notch信号,由Eogt和O-GlcNAc甘氨酸支持,在Pofut1缺席时,对于肠道活力至关重要.
结论:
- 无论是O-fucose和O-GlcNAc甘氨酸都对小鼠肠道中的Notch信号提供了基本的支持.
- 通过EOGT介导的O-GlcNAc糖化提供了必要的残留Notch信号,支持Pofut1缺乏小鼠的生存能力.
- 这些发现为O-甘氨酸在诺奇带结合和信号传导中的调节作用提供了新的见解.
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