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在小鼠中,TMC7 缺乏导致了宏体生物发生缺陷和男性不孕症
Jing Wang1,2, Yingying Yin1,3, Lei Yang1,2
1Key Laboratory of Experimental Teratology, Ministry of Education, Department of Cell Biology, School of Basic Medical Sciences, Shandong University, Jinan, China.
eLife
|September 13, 2024
概括
跨膜通道类7 (TMC7) 蛋白对于精子发育至关重要. 丧失TMC7会通过破坏离子稳态和增加氧化应激来损害宏粒体的形成和精子质量.
科学领域:
- 细胞生物学 细胞生物学
- 生殖生物学 生殖生物学
- 离子通道功能的功能
背景情况:
- 跨膜通道类 (TMC) 蛋白质形成了一个保存的离子通道家族.
- 已知TMC1和TMC2是参与听觉的机械传导通道.
- 包括TMC7在内的其他TMC蛋白的功能在很大程度上没有被描述.
研究的目的:
- 研究TMC7在哺乳动物生殖中的生理作用.
- 阐明TMC7在精子生成中的功能背后的分子机制.
主要方法:
- 对Tmc7淘汰赛 (Tmc7-/-) 小鼠的分析.
- 免疫光显微镜用于评估蛋白质定位 (TMC7,GM130).
- 评价精子形态,体形成和线粒体组织.
- 评估细胞内离子稳态和反应性氧物种 (ROS) 水平.
主要成果:
- TMC7在丸中得到特定的表达,并且在精子生成过程中对体生物发生是必不可少的.
- Tmc7-/-小鼠表现出异常的精子头形态,混乱的线粒体外,并减少了延长的精子.
- TMC7局限于cis-Golgi区域,其缺乏会破坏Golgi形态和囊泡融合.
- TMC7的损失导致离子稳态受损,ROS水平增加,以及随后的戈尔吉和内质网膜应激.
结论:
- TMC7在维持 pH 和离子恒温中起着至关重要的作用,这是适当的宏生物生成所必需的.
- TMC7对于精子的发育和质量至关重要,突出了其在精子生成中的新功能.
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