Sperm membrane proteins DCST1 and DCST2 are required for sperm-egg interaction in mice and fish.

Sperm membrane proteins DCST1 and DCST2 are required for sperm-egg interaction in mice and fish.
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DOI:
10.1038/s42003-022-03289-w
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发表时间:
2022-04-07
影响因子:
5.9
通讯作者:
Ikawa M
Ikawa M
中科院分区:
生物学2区
文献类型:
--
作者:
Noda T;Blaha A;Fujihara Y;Gert KR;Emori C;Deneke VE;Oura S;Panser K;Lu Y;Berent S;Kodani M;Cabrera-Quio LE;Pauli A;Ikawa M

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精卵融合的过程是成功受精的关键,然而在脊椎动物中调控这些步骤的潜在机制尚不清楚。在这里,我们发现小鼠和斑马鱼的DCST1和DCST2在精子中都是使卵子受精所必需的,类似于它们在C. elegans中的同源物SPE-42和SPE-49以及D. melanogaster中的Sneaky。小鼠Dcst1和Dcst2单敲除(KO)精子能够进行顶体反应,并显示出正常的IZUMO1重新定位到赤道段,IZUMO1是精子-卵子融合的重要因素。虽然两种单一KO精子都能与卵膜结合,但它们表现出融合缺陷,导致Dcst1 KO雄性几乎不育,而Dcst2 KO雄性不育。与小鼠相似,斑马鱼dcst1 KO雄性是低生育能力的,而dcst2和dcst1/2双KO雄性是不育的。斑马鱼的dst1 /2 KO精子是有活力的,可以接近卵子,但在与胚膜结合方面存在缺陷。此外,我们发现DCST1和DCST2相互作用,相互依赖。这些数据表明,DCST1/2对两种脊椎动物的雄性生殖能力至关重要,突出了它们在受精过程中作为保守因子的重要作用。精子膜蛋白DCST1和DCST2在配子融合中的作用扩展到斑马鱼,表明这些相互依赖的蛋白是精子-卵子结合所必需的。
The process of sperm-egg fusion is critical for successful fertilization, yet the underlying mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 in C. elegans and Sneaky in D. melanogaster. Mouse Dcst1 and Dcst2 single knockout (KO) sperm are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO sperm can bind to the oolemma, they show the fusion defect, resulting that Dcst1 KO males become almost sterile and Dcst2 KO males become sterile. Similar to mice, zebrafish dcst1 KO males are subfertile and dcst2 and dcst1/2 double KO males are sterile. Zebrafish dcst1/2 KO sperm are motile and can approach the egg, but are defective in binding to the oolemma. Furthermore, we find that DCST1 and DCST2 interact with each other and are interdependent. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species, highlighting their crucial role as conserved factors in fertilization. The role of sperm membrane proteins DCST1 and DCST2 in gamete fusion is extended to zebrafish in showing that these interdependent proteins are required for sperm-egg binding.
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