主要毛在小鼠决定化过程中阻止cGAS-STING通路的激活
Bo Li1,2, Yu-Ying He2, Wen-Xu Yao1
1Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountain Region, College of Animal Science, Guizhou University, Guiyang, 550025, China.
Communications biology
|April 14, 2025
概括
主要毛通过保持核完整性来调节决定性. 毛损失会导致DNA泄漏,激活cGAS-STING通路并影响怀孕.
科学领域:
- 细胞生物学 细胞生物学
- 生殖生物学 生殖生物学
- 器官的功能 器官的功能
背景情况:
- 初级毛是发育和恒温的关键信号中心.
- 脱二化对于成功怀孕至关重要.
- 在怀孕期间,初级乳毛在子宫内膜 stromal 细胞中的作用是未知的.
研究的目的:
- 为了研究小鼠决定化过程中初级毛的作用.
- 在这个过程中识别主要毛功能的主要调节者.
- 阐明将乳毛与决定化联系起来的分子机制.
主要方法:
- 利用具有影响初级乳毛细胞的遗传变异的小鼠模型.
- 研究了纤毛损失对actomyosin细胞骨和核完整性的影响.
- 分析了循环GMP-AMP合成酶 (cGAS) -STING通路的激活.
- 采用药理干预来调节细胞骨和信号通路.
主要成果:
- TMEM67是一种纤毛过渡区蛋白质,对于决定化至关重要.
- 失去了初级毛会导致actomyosin收缩,核膜损伤和微核的形成.
- 将DNA泄漏到微核中会激活cGAS-STING通路,从而减少CCL6并损害决定化.
- 抑制行为蛋白或RhoA-ROCK信号传递可以挽救纤毛发育,核完整性和决定性.
结论:
- 初级乳毛通过调节actin细胞骨架来维持核完整性.
- 防止DNA通过完整的乳毛泄漏对于抑制异常cGAS-STING通路激活至关重要.
- 这种机制突显了初级乳毛,核稳定性和怀孕期间免疫信号之间的新联系.
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