School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, China.
Department of Physiology, Wayne State University, Detroit, Michigan, USA.
Biol Reprod. 2019 Jul 1;101(1):188-199. doi: 10.1093/biolre/ioz071.
Intraflagellar transport protein 74 (IFT74) is a component of the core intraflagellar transport complex, a bidirectional movement of large particles along the axoneme microtubules for cilia formation. In this study, we investigated its role in sperm flagella formation and discovered that mice deficiency in Ift74 gene in male germ cells were infertile with low sperm count and immotile sperm. The few developed spermatozoa displayed misshaped heads and short tails. Transmission electron microscopy revealed abnormal flagellar axonemes in the seminiferous tubules where sperm are made. Clusters of unassembled microtubules were present in the spermatids. Testicular expression levels of IFT27, IFT57, IFT81, IFT88, and IFT140 proteins were significantly reduced in the conditional Ift74 mutant mice, with the exception of IFT20 and IFT25. The levels of outer dense fiber 2 and sperm-associated antigen 16L proteins were also not changed. However, the processed A-Kinase anchor protein, a major component of the fibrous sheath, a unique structure of sperm tail, was significantly reduced. Our study demonstrates that IFT74 is essential for mouse sperm formation, probably through assembly of the core axoneme and fibrous sheath, and suggests that IFT74 may be a potential genetic factor affecting male reproduction in man.
内鞭毛运输蛋白 74（IFT74）是核心内鞭毛运输复合物的一个组成部分，该复合物是沿着鞭毛轴丝进行的大颗粒的双向运动，用于纤毛的形成。在这项研究中，我们研究了它在精子鞭毛形成中的作用，发现男性生殖细胞中 Ift74 基因缺失的小鼠不育，精子数量少且运动能力差。少数发育成熟的精子显示出头畸形和短尾。透射电子显微镜显示，在精子形成的生精小管中，鞭毛轴丝异常。未组装的微管簇存在于精母细胞中。条件性 Ift74 突变小鼠的睾丸中 IFT27、IFT57、IFT81、IFT88 和 IFT140 蛋白的表达水平显著降低，但 IFT20 和 IFT25 除外。外致密纤维 2 和精子相关抗原 16L 蛋白的水平也没有改变。然而，处理过的 A-激酶锚蛋白（AKAP），精子尾部特有的纤维鞘的主要成分，显著减少。我们的研究表明，IFT74 对于小鼠精子的形成是必不可少的，可能是通过核心轴丝和纤维鞘的组装，这表明 IFT74 可能是影响人类男性生殖的一个潜在遗传因素。
