Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871 Japan.
Graduate School of Medicine, Osaka University, Suita, Osaka 5650871 Japan.
Sci Adv. 2023 Jan 25;9(4):eade7607. doi: 10.1126/sciadv.ade7607.
Spermatozoa need to undergo an exocytotic event called the acrosome reaction before fusing with eggs. Although calcium ion (Ca) is essential for the acrosome reaction, its molecular mechanism remains unknown. Ferlin is a single transmembrane protein with multiple Ca-binding C2 domains, and there are six ferlins, dysferlin (DYSF), otoferlin (OTOF), myoferlin (MYOF), fer-1-like 4 (FER1L4), FER1L5, and FER1L6, in mammals. , , and knockout mice have been generated, and each knockout mouse line exhibited membrane fusion disorders such as muscular dystrophy in , deafness in , and abnormal myogenesis in . Here, by generating mutant mice of , , and , we found that only is required for male fertility. mutant spermatozoa could migrate in the female reproductive tract and reach eggs, but no acrosome reaction took place. Even a Ca ionophore cannot induce the acrosome reaction in mutant spermatozoa. These results suggest that FER1L5 is the missing link between Ca and the acrosome reaction.
精子在与卵子融合之前需要经历一个称为顶体反应的胞吐事件。尽管钙离子（Ca）对于顶体反应是必不可少的，但它的分子机制仍不清楚。Ferlin 是一种具有多个 Ca 结合 C2 结构域的单一跨膜蛋白，哺乳动物中有六种 Ferlin，分别是 dysferlin (DYSF)、otoferlin (OTOF)、myoferlin (MYOF)、fer-1-like 4 (FER1L4)、FER1L5 和 FER1L6。已经生成了 、 和 的敲除小鼠，每种敲除小鼠系均表现出膜融合障碍，如 中的肌肉营养不良、 中的耳聋和 中的异常肌生成。在这里，通过生成 、 和 的突变小鼠，我们发现只有 对于雄性生育力是必需的。 突变精子能够在雌性生殖道中迁移并到达卵子，但没有发生顶体反应。即使使用钙离子载体也不能诱导 突变精子发生顶体反应。这些结果表明 FER1L5 是 Ca 和顶体反应之间缺失的环节。
