细胞球蛋白在发育过程中调节NO依赖的乳毛和器官横向性
Elizabeth R Rochon1, Jianmin Xue2, Manush Sayd Mohammed3
1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Nature communications
|December 14, 2023
概括
细胞球蛋白对于正确的乳毛功能和器官发育至关重要. 这种血红蛋白调节氧化信号通路,这对于斑马鱼的左右图案和小鼠的呼吸道乳头至关重要.
科学领域:
- 生物化学 生化学
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 细胞球蛋白 (CYGB) 是一种血红蛋白,其生理作用尚不清楚.
- 人类与状腺功能障碍和低氧化 (NO) 生产相关的疾病包括左右心脏决定缺陷.
- 斑马鱼细胞球蛋白 (cygb2) 的遗传删除导致心脏发育异常.
研究的目的:
- 调查细胞蛋白的生理功能,特别是其在乳毛功能和器官横向性中的作用.
- 阐明细胞质球蛋白与氧化信号传递有关的功能背后的分子机制.
主要方法:
- 使用斑马鱼 (cygb2) 突变体和细胞蛋白淘汰小鼠模型.
- 研究了Cygb2与乳毛和氧化合成酶 (Nos2b) 的同定位.
- 评估眼的结构和功能,器官的横向性和氧化水平.
主要成果:
- 发现Cygb2与斑马鱼Kupffer囊泡中的毛和Nos2b共同定位,在cygb2突变体中破坏了毛结构和功能.
- 缺陷的No2b或瓜尼酸环酶 (gucy1a) 拷贝的状和横向性缺陷.
- 缺陷被NO捐赠者,酸环酶刺激剂或斑马鱼中的Nos2b过度表达所拯救.
- 细胞球蛋白淘汰赛小鼠表现出呼吸道乳毛结构受损和NO水平降低.
结论:
- 细胞质蛋白作为氧化合成酶-溶于酸环酶-循环GMP信号通路的积极调节者.
- 这条通路对于正常的乳毛运动和左右模式至关重要.
- 细胞球蛋白在NO信号传递中的作用在各物种中保持不变,影响胚胎发育和呼吸道功能.
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