The gamete fusion process is defective in eggs of Cd9-deficient mice
The gamete fusion process is defective in eggs of Cd9-deficient mice
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DOI：
10.1038/73502
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发表时间：
2000-03-01
期刊：
影响因子：
30.8
通讯作者：
Kudo, A
中科院分区：
文献类型：
--
作者：
Kaji, K;Oda, S;Kudo, A
细胞表面分子Cd 9是跨膜-4超家族的成员（1），与整联蛋白家族（2）和其他膜蛋白（3-5）相互作用，并被认为参与细胞迁移和粘附（6-8）。Cd 9的表达增强肌细胞之间的膜融合（9），并促进某些细胞中的病毒感染（10，11）。受精也涉及配子之间的膜融合。在哺乳动物中，精子与卵子表面的微绒毛结合，精卵膜融合首先发生在精子头部的赤道区周围（12）。然后，融合的膜被破坏，精子核和细胞质被整合到卵子中。Cd 9在小鼠卵子的质膜上表达，抗Cd 9单克隆抗体抑制精卵表面相互作用（13）。我们产生了Cd 9（-/-）小鼠，发现纯合子突变的女性不育。精卵结合是正常的，但精子-卵子融合几乎完全抑制卵子从Cd 9（-/-）的女性。细胞内Ca 2+振荡，这信号受精，几乎所有的突变卵，在罕见的情况下，反应发生后很长一段时间。在正常动物中，Cd 9分子表达在卵微绒毛上，并在精子附着部位变得密集。因此，我们的研究结果表明，Cd 9是重要的配子融合过程中受精。
The cell-surface molecule Cd9, a member of the transmembrane-4 superfamily(1), interacts with the integrin family(2) and other membrane proteins(3-5), and is postulated to participate in cell migration and adhesion(6-8). Expression of Cd9 enhances membrane fusion between muscle cells(9) and promotes viral infection in some cells(10,11). Fertilization also involves membrane fusion, between gametes. In mammals, the sperm binds to microvilli on the egg surface, and sperm-egg membrane fusion first occurs around the equatorial region of the sperm head(12). The fused membrane is then disrupted, and the sperm nucleus as well as the cytoplasm is incorporated into the egg. Cd9 is expressed on the plasma membrane of the mouse egg, and an anti-Cd9 monoclonal antibody inhibits sperm-egg surface interactions(13). We generated Cd9(-/-) mice and found that homozygous mutant females were infertile. Sperm-egg binding was normal, but sperm-egg fusion was almost entirely inhibited in eggs from Cd9(-/-) females. Intracellular Ca2+ oscillations, which signal fertilization, were absent in almost all mutant eggs; in rare cases, a response occurred after a long time period. In normal animals, Cd9 molecules were expressed on the egg microvilli and became densely concentrated at the sperm attachment site. Thus, our results show that Cd9 is important in the gamete fusion process at fertilization.