The vertebrate- and testis- specific transmembrane protein C11ORF94 plays a critical role in sperm-oocyte membrane binding.
The vertebrate- and testis- specific transmembrane protein C11ORF94 plays a critical role in sperm-oocyte membrane binding.
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DOI：
10.1186/s43556-022-00092-1
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发表时间：
2022-09-02
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4
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精卵膜融合是哺乳动物受精的必要条件。决定精子与卵母细胞融合的因素在很大程度上是未知的。到目前为止，精子因子IZUMO1和卵母细胞膜上的IZUMO1对抗受体JUNO已被确定为需要融合的蛋白。一些精子膜蛋白如FIMP、SPACA6和TEME95已被证明不直接调节融合，但敲除它们会影响精子和卵母细胞的融合过程。在这里，我们发现了一个新的基因C11orf94编码睾丸特异性小跨膜蛋白，该蛋白出现在脊椎动物中，可能是通过细菌的水平基因转移获得的，在精卵结合中起着不可或缺的作用。我们证明了C11orf94的缺失显著降低了小鼠的雄性生育能力。c11orf94缺陷小鼠的精子可以通过透明带，但不能与卵母细胞膜结合，在卵泡周围空间积累。与此一致的是，将c11orf94缺陷小鼠的精子微注射到卵母细胞细胞质中，获得受精的卵母细胞并正常发育为囊胚。蛋白质组学分析显示，C11orf94影响了多种已知精卵结合和融合不可或缺的基因产物的表达，包括IZUMO1、EQTN和CRISP1。因此，我们的研究表明，C11ORF94是一种脊椎动物和睾丸特异性的小跨膜蛋白，在精子与膜结合中起关键作用。在线版本包含补充资料，下载地址：10.1186/s43556-022-00092-1。
Sperm-oocyte membrane fusion is necessary for mammalian fertilization. The factors that determine the fusion of sperm with oocytes are largely unknown. So far, spermatozoon factor IZUMO1 and the IZUMO1 counter-receptor JUNO on the oocyte membrane has been identified as a protein requiring fusion. Some sperm membrane proteins such as FIMP, SPACA6 and TEME95, have been proved not to directly regulate fusion, but their knockout will affect the fusion process of sperm and oocytes. Here, we identified a novel gene C11orf94 encoding a testicular-specific small transmembrane protein that emerges in vertebrates likely acquired via horizontal gene transfer from bacteria and plays an indispensable role in sperm-oocyte binding. We demonstrated that the deletion of C11orf94 dramatically decreased male fertility in mice. Sperm from C11orf94-deficient mice could pass through the zona pellucida, but failed to bind to the oocyte membrane, thus accumulating in the perivitelline space. In consistence, when the sperm of C11orf94-deficient mice were microinjected into the oocyte cytoplasm, fertilized oocytes were obtained and developed normally to blastocysts. Proteomics analysis revealed that C11orf94 influenced the expression of multiple gene products known to be indispensable for sperm-oocyte binding and fusion, including IZUMO1, EQTN and CRISP1. Thus, our study indicated that C11ORF94 is a vertebrate- and testis-specific small transmembrane protein that plays a critical role in sperm binding to the oolemma. The online version contains supplementary material available at 10.1186/s43556-022-00092-1.