双双酸酶辅因子UAF1与USP1相互作用,在精子发生过程中起着重要作用
Ziqi Wang1,2,3,4, Tongtong Li1,2, Dongkai Liu1,2,3,4
1Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China.
iScience
|April 9, 2024
概括
UAF1对于男性的生育能力至关重要,通过USP1二维基因酶复合体调节精子生成. 缺少它会破坏精子发育所必需的关键蛋白质水平.
科学领域:
- 生殖生物学 生殖生物学
- 分子细胞生物学 分子细胞生物学
- 生物化学 生物化学
背景情况:
- 精子生成是男性生殖细胞分化的最后阶段,对男性生育能力至关重要.
- 在精子发生过程中二维基因的作用尚不清楚.
- 脱化酶涉及到各种细胞过程,包括生殖细胞的发育.
研究的目的:
- 为了研究UAF1在小鼠精子生成中的功能.
- 阐明UAF1影响男性生殖细胞分化的机制.
- 为了识别丸中与UAF1相互作用的deubiquitinating酶.
主要方法:
- 使用Stra8-Cre敲入小鼠菌株 (Uaf1 sKO) 在前胚性生殖细胞中选择性删除UAF1.
- 在小鼠丸中分析UAF1-USP1相互作用和同位素.
- 基于Tandem质量标签 (TMT) 的蛋白质组学,以识别Uaf1淘汰丸中的蛋白质水平变化.
主要成果:
- 在生殖细胞中Uaf1的缺失导致精子发生障碍和男性不孕.
- 在丸中,UAF1与USP1相互作用和同位.
- UAF1缺乏导致蛋白质水平的改变和USP1.1的局部化.
- 蛋白质组分析显示Uaf1淘汰赛丸中精子生成必需蛋白质水平降低.
结论:
- UAF1/USP1二维基因酶复合体对于正常的精子发生是必不可少的.
- UAF1通过控制关键的精子生成相关蛋白质的水平来调节精子生成,可能是通过USP1.
- 这项研究强调了UAF1在男性生殖细胞分化和生育能力方面的关键作用.
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