Evolutionarily conserved sperm factors, DCST1 and DCST2, are required for gamete fusion.
Evolutionarily conserved sperm factors, DCST1 and DCST2, are required for gamete fusion.
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作者：
Inoue N;Hagihara Y;Wada I
为了触发配子融合，精子需要激活分子机制，其中精子 IZUMO1 和卵母细胞 JUNO (IZUMO1R) 的相互作用在哺乳动物中发挥着关键作用。尽管最近已经确定了参与这一过程的一系列因素，但尚未报道可在脊椎动物和无脊椎动物中发挥作用的共同因素。在这里，我们首先通过基因破坏和互补实验证明，进化上保守的因子树突状细胞表达的七跨膜蛋白结构域1（DCST1）和树突状细胞表达的七跨膜蛋白结构域2（DCST2）对于小鼠精卵融合至关重要。我们还发现另一种配子融合相关精子因子SPACA6的蛋白质稳定性受到DCST1/2和IZUMO1的不同调节。因此，我们认为精子通过整合各种分子途径来确保哺乳动物的适当受精，包括经过近十亿年进化而发展起来的进化保守系统。
To trigger gamete fusion, spermatozoa need to activate the molecular machinery in which sperm IZUMO1 and oocyte JUNO (IZUMO1R) interaction plays a critical role in mammals. Although a set of factors involved in this process has recently been identified, no common factor that can function in both vertebrates and invertebrates has yet been reported. Here, we first demonstrate that the evolutionarily conserved factors dendrocyte expressed seven transmembrane protein domain-containing 1 (DCST1) and dendrocyte expressed seven transmembrane protein domain-containing 2 (DCST2) are essential for sperm–egg fusion in mice, as proven by gene disruption and complementation experiments. We also found that the protein stability of another gamete fusion-related sperm factor, SPACA6, is differently regulated by DCST1/2 and IZUMO1. Thus, we suggest that spermatozoa ensure proper fertilization in mammals by integrating various molecular pathways, including an evolutionarily conserved system that has developed as a result of nearly one billion years of evolution.