Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice.
Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice.
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鞭毛内转运蛋白 IFT20 对于小鼠雄性生育力和精子发生至关重要
DOI：
10.1091/mbc.e16-05-0318
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发表时间：
2016-09-28
影响因子：
3.3
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhang Z;Li W;Zhang Y;Zhang L;Teves ME;Liu H;Strauss JF 3rd;Pazour GJ;Foster JA;Hess RA;Zhang Z
鞭毛内转运蛋白IFT20在雄性生殖细胞发育中的研究表明，它对小鼠雄性生殖和精子发生至关重要，在精子鞭毛的形成和细胞质成分的处理中发挥作用。鞭毛内运输（IFT）是一种保守的机制，被认为是纤毛和鞭毛的组装和维持所必需的。然而，人们对其在哺乳动物精子鞭毛形成中的作用知之甚少。为了填补这一空白，我们破坏了男性生殖细胞中的Ift20基因。纯合子突变小鼠不育，精子数量和活力显著降低。此外，在精管腔内发现形状异常的、细长的精细胞头和球状的、圆形的精细胞。电镜显示细胞质囊泡增多，纤维样结构，线粒体异常积聚，成熟溶酶体减少。少数发育的精子轴突被破坏，鞭毛上保留了一些细胞质叶成分。ODF2和SPAG16L这两种精子鞭毛蛋白在突变小鼠的精子尾部无法结合，而在没有IFT20的情况下，这两种蛋白在生殖细胞中组装成密度较低的复合物。破坏IFT20并没有显著改变IFT88 （IFT-B复合体的组成部分）和IFT140 （IFT-A复合体的组成部分）的表达水平。尽管IFT20突变小鼠睾丸中与IFT20相关的自噬核心蛋白ATG16的表达水平降低，但其他主要自噬标志物，包括LC3和泛素的表达水平没有改变。我们的研究表明，IFT20对小鼠雄性生殖和精子发生至关重要，其主要功能是为精子鞭毛的形成运输货物蛋白。它似乎也参与去除多余的细胞质成分。
Study of intraflagellar transport protein IFT20 in male germ cell development shows that it is essential for male fertility and spermiogenesis in mice, playing a role in the building of sperm flagella and the disposal of cytoplasmic components. Intraflagellar transport (IFT) is a conserved mechanism believed to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile, with significantly reduced sperm counts and motility. In addition, abnormally shaped, elongating spermatid heads and bulbous, round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria, and a decrease in mature lysosomes. The few developed sperm had disrupted axonemes, and some retained cytoplasmic lobe components on the flagella. ODF2 and SPAG16L, two sperm flagella proteins, failed to be incorporated into sperm tails of the mutant mice, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of the IFT-B complex, and IFT140, a component of the IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin, were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components.